Strains with cytoplasmically and nuclearly inherited antibiotic-resistant markers were tested for cross resistance to diverse inhibitors of mitochondrial function. Five independently isolated nuclear markers were observed to result in resistance to chloramphenicol, tetracycline, oligomycin, antimycin A, carbonylcyanide-m-chlorophenylhydrazone, and triphenylmethylphosphonium bromide; these same strains were sensitive to erythromycin, neomycin, and ethidium bromide. In contrast, 11 strains carrying cytoplasmically inherited resistance markers were not cross resistant to any unrelated chemical inhibitors. It is suggested that the nuclear mutations are expressed as general membrane mutants whereas mitochondrial DNA codes for more specific mitochondrial functions.