Yeast mutants with genetically altered mitochondria are extremely useful in the study of oxidative phosphorylation mechanisms (Beck et al., 1968). Such mutants are usually detected by their inability to grow on non-fermentable carbon sources, their spectral characteristics, and by selective staining. Drug resistance has also been employed in obtaining mitochondrial mutants (Thomas and Wilkie, 1968; Butow and Zeydel, 1968), but as yet this method has not been extended to include specific inhibitors of oxidative phosphorylation. This report describes the isolation of 50 oligomycin-resistant Saccharomyces cerevisiae mutants and the genetic characterization of two of these mutants and a naturally resistant strain. At least two Mendelian genes control the resistance in these strains. Resistance displays partial dominance and additivity in heterozygous diploids. Oligomycin partially inhibits cytochrome synthesis, and increases the frequency of mutation to cytoplasmic respiratory deficiency (p-). Oligomycin resistance is accompanied by resistance to venturicidin. © 1968.