When choosing an avenue of attack during the Isolation stage, it's important to keep in mind two different dimensions: probability and testability.? Probability is your informed estimate of how likely you believe a particular problem is the cause. Testability is how much time and effort you suspect it will take to rule that particular cause in or out.? Ideally, your most probable causes would be the most testable, but it rarely works out so nicely.? Ultimately, you have a simple 2x2 matrix of possibilities, and you can place each theory in one of the sectors:

The first theories to try are of course the Highly Probable-Easily Testable ones,? labeled "Ideal" in the matrix.? Next is a judgement call.? If you have some very Easily Testable theories that are fairly Improbable, it might make sense to take an hour to knock them all out.? These are labeled "Why Not?". On the other hand, if you have a Highly Probable theory that might take some effort to test, it could be much more valuable. These are labeled "Necessary Evil".? Finally, if you've exhausted all other possibilities, it's time for the Low Probability and Hard to Test theories, labeled "Last Resort".? Before you start trying to follow up on these ones, take another long look at what has already been tried, the data you've already collected, and any other information that might help you see a glimmer of another possibility before wasting a lot of effort on an unlikely theory.? However, sometimes there's no other choice.
Rather than just assigning a label to each theory, it can also help to simply draw out the matrix above and plot your theories on an X/Y axis, where upper-left is best and lower-right is worst.? This can help you easily see both where you ought to start, and how much work you are in for before starting in on an extended isolation exercise.