I get the whine even if the Edirol card is not plugged into the mixer, but not if the monitors are not plugged into the mixer. I currently have unbalanced cables from the mixer to my monitors.
I have to use the internal word clock. When any music is playing, it easily drowns out the whine, but I'd rather get to the source of the problem and sort it out.
SOS Forum Post
PC music specialist Martin Walker replies: If you're getting interference even when your soundcard isn't plugged into the mixer, but it stops when you disconnect the mixer from your speakers, it doesn't sound like a problem with the soundcard itself, although you may well be hearing sounds that originally come from the soundcard, probably from its word clock.
As you can hear the interference even when the connection between the soundcard and mixer is broken, I suspect that you're suffering from a ground loop problem which is causing background digital noises to be heard — contrary to popular opinion, ground loops don't only cause background hum. Once there are multiple earth paths, noises from mouse movements, hard drive accesses, and graphic redraws can become audible in the background. Breaking the loop normally results in these all disappearing.
If you have the option of fitting balanced cables anywhere in the chain (mixer to monitors, and soundcard to mixer) this should cure the problem, so try this first.
It could also help if you plug everything into one mains socket via a distribution board, since this will generally make any existing ground loop smaller. It's also worth reseating your soundcard in its socket and tightening down its backplate screw. This ensures a good earth connection from soundcard to the PC chassis.
Active monitors can be a source of problems because they are earthed via their mains lead and via the audio input lead. This is why using balanced connections helps.
However, the only sure way to completely cure ground loop problems is to temporarily unplug all your audio cables and start from scratch. First listen to your powered monitors to make sure they don't exhibit any background noises with nothing connected to their audio inputs (sometimes US models with transformers designed for 60Hz will buzz when running on 50Hz). Then connect the stereo outputs from your mixer to the monitors and check again — if you have the option to use balanced I/O, do so.
Finally, connect the inputs of your mixer one by one to your various synths and soundcard devices with them powered up, temporarily turning up the mixer output volume fairly high after each one is plugged in to see when any hums or buzzes appear. As soon as you hear any noises you've found the offending connection, and can either try making up special pseudo-balanced cables if your mixer has balanced inputs and the source is unbalanced, or trying a line-level DI (Direct Injection) box between the device and the mixer input.