The alcohol dehydrogenases in yeast form one of the best-understood eukaryotic regulatory systems at the genetic level, but very little is known about their regulation at the biochemical level. We report on a simple whole-cell assay system for the induction of the inducible isozyme, alcohol dehydrogenase II, which has been used to show that no single compound added to the medium is responsible for the induction. The compounds which show the greatest inducing activity--malate, glutamate and fumarate--are all directly or indirectly involved in mitochondrial transport systems. No single compound can be purified from extracts of yeast cells to give inducing activity at low concentrations, suggesting that the inducing activity is an endogenous function of the cell. Tentative models for regulation of this isozyme involving the mitochondrion are proposed, and suggestions are made for testing these models further.