In this paper, I argue (i) that there are certain methodological practices that are epistemically significant, and (ii) that we can test for the success of these practices empirically by examining case-studies in the history of science. Analysing a particular episode from the history of medicine, I explain how this can help us resolve specific cases of underdetermination. I conclude that, while the anti-realist is (more or less legitimately) able to construct underdetermination scenarios on a case-by-case basis, he will have to abandon the strategy of using algorithms to do so, thus losing the much needed guarantee that there will always be rival cases of the required kind.