Whether recording or playing back, the sound starts breaking up irregularly, sometimes infrequently, sometimes more frequently, as I add plug-ins, even at 48K sample rate. I'm using ASIO drivers. Sometimes it sounds like listening to someone on their cell phone with a spotty signal. At its worst, it sounds like a Geiger counter going crazy, particularly when I add in Guitar Rig or Bias Fx (both 64 bit) along with a track of Dim Pro and one of Session Drummer or Addictive Drums. I have Platinum 64 bit on an HP desktop with Windows 7 and 6-core processor - 3.2 GHz - with 16 GB RAM. Hitachi platter drive at 7200 rpm, however pulling sound files from My Book 3TB external hard drive. Using MOTU Ultralite mk3 Firewire Interface for guitars. When I bounce an entire mix, the mix breaks up as well on playback, however when I convert mix to mp3, no hint  of the breakups. Someone suggested my RAM was bad so I swapped out RAM cards - no change. Someone else has suggested trying an internal solid state drive but I would prefer to not go to that expense if that's not the problem. Any ideas out there? Thanks in advance for your feedback.

Increase buffer size.

Welcome to the forum!
 
Your asio buffer settings are most likely the problem. They are at the very least a good place to start.
 
https://www.cakewalk.com/Support/Knowledge-Base/2007013007/Audio-Dropouts-Clicks-and-Pops-When-Playing-and-Recording
 

Threes a charm - increase buffer :-)

Four on the floor - increase buffer size...

I typically record with my ASIO Buffer Size of my interface set to 128.  I could go lower, but since I don't hear any lag at that setting, I leave it there and it just works, wonderfully.
 
When I finish recording and move on to mixing, I then raise the size of my ASIO Buffer Size to either 1024 or 2048, so that I can load up a bunch of effects, some of which require a large buffer to process signal correctly.  Since I am not trying to record anything at this point, the large buffer will take a few moments to start playback, but that doesn't matter - having enough buffer size for the effects processing is what matters at that stage.
 
If you are still having audio quality issues running with a buffer size around 128 when recording, I would suggest you perform a simple test - hit the letter 'E' on your computer keyboard, and that will toggle a bypass of all effects.  If your audio quality issues vanish, then one or more of your effects is likely NOT meant to be used during recording, but instead is meant to be used during MIXING, where a super large buffer setting will allow that effect to work properly.  (After testing, hit 'E' again to toggle off the effects bypassing).
 
So, IF the above demonstrates issues with one or more of the effects - look for 'leaner' effects to be used while recording, and then swap them back out during mixing, for the more robust ones.  Effects that add a bunch of latency or otherwise chew up a lot of CPU are the ones to watch out for - like a convoluted reverb, or linear phase types. (Perfect Space, Boost 11, etc.)
 
Bob Bone

Thanks very much, everybody, for your feedback and for the link to the Dropouts section at Product Support. I read that thoroughly. I was running my buffers at 512 already but bumped it up to 1024 and it reduced drops and stutters some. Went to 2048 and no change from 1024. Going to download the DPC Latency Checker to see if a problem with DPC Latency Spikes although I'm not running on a laptop and don't have a WiFi adapter on my desktop. Thing is, from my limited perspective, I'm not doing an extensive production on the tune I'm working on. Acoustic guitar with compression, EQ and reverb. Dim Pro fingered bass with EQ and compression. Dim Pro drawn bass with no fx. Electric guitar with Bias FX plug-in. Session drummer no fx so far. Compression on Master channel. Interestingly, I can turn off Bias Fx only and it goes away. I can run Bias Fx and turn off everything else and it comes back. On another piece using Guitar Rig, Dim Pro, Session Drummer and Rapture, I get a wider variation of problems as I turn things on and off. Otherwise, disconnected from Internet, antivirus/malware deactivated. I do have a hammer in the garage that I haven't tried yet. It fixes cars sometimes! Will report back on results. Thanks again!

GuitarSIU12
Thanks very much, everybody, for your feedback and for the link to the Dropouts section at Product Support. I read that thoroughly. I was running my buffers at 512 already but bumped it up to 1024 and it reduced drops and stutters some. Went to 2048 and no change from 1024. Going to download the DPC Latency Checker to see if a problem with DPC Latency Spikes although I'm not running on a laptop and don't have a WiFi adapter on my desktop. Thing is, from my limited perspective, I'm not doing an extensive production on the tune I'm working on. Acoustic guitar with compression, EQ and reverb. Dim Pro fingered bass with EQ and compression. Dim Pro drawn bass with no fx. Electric guitar with Bias FX plug-in. Session drummer no fx so far. Compression on Master channel. Interestingly, I can turn off Bias Fx only and it goes away. I can run Bias Fx and turn off everything else and it comes back. On another piece using Guitar Rig, Dim Pro, Session Drummer and Rapture, I get a wider variation of problems as I turn things on and off. Otherwise, disconnected from Internet, antivirus/malware deactivated. I do have a hammer in the garage that I haven't tried yet. It fixes cars sometimes! Will report back on results. Thanks again!

Have you tried freezing the track?
 
Dan

If I am reading the OP correctly, the projects are located on a slow external drive. If this is the case, try moving the project to the internal drive or better still install a second drive in the desktop. It would not have to be an SSD, a second conventional 7200RPM hard drive would be better than running from the MyBook. This

GuitarSIU12
 even at 48K sample rate

suggests attempts at higher sample rates. I doubt the external drive would be up to that challenge at all.

I have one of those 3tb My Book drives. While I don't use it for my project drive (it's the back-up), I have experimented with it. Through usb 3 it absolutely can handle large SONAR projects without any problem.