The two unlinked genes CYCI and CYC7 encode iso-l-cytochrome c and iso-2-cytochrome c, respectively, in the yeast Saccharomyces cerevisiae. An examination of the steady-state level of CYCI and CYC7 mRNAs in normal and mutant strains grown under different conditions, along with previous results of apoprotein levels, demonstrate that CYCI and CYC7 have similar and different modes of regulation. Both CYCI and CYC7 mRNAs are diminished after anaerobic growth. In contrast, CYCI mRNA but not CYC7 mRNA is decreased by heme deficiency in hem) mutants. Although both CYCI and CYC7 mRNAs are substantially lowered after growth in glucose medium, there is a difference in the kinetics of glucose derepression. CYCI mRNA levels rise in the early logarithmic phase of growth before complete exhaustion of glucose, whereas CYC7 mRNA levels rise in the late logarithmic phase when the level of CYCI mRNA has plateaued. For a brief period before cessation of growth, the level of CYC7 mRNA attains a level corresponding to the high derepressed level of CYCJ mRNA. The high amount of CYC7 mRNA is surprising because iso-2-cytochrome c constitutes only 5% of the total cytochrome c complement in derepressed cells. We suggest that iso-2-cytochrome c has the potential to comprise a major proportion of cytochrome c under certain physiologic conditions that have not been experimentally defined. The cyc3 mutant, which lacks the ability to attach heme groups to apocytochromes c, contains both CYCI and CYC7 mRNAs in normal amounts. Yet, cyc3 mutants contain only apoiso-2-cytochrome c and not apoiso-1-cytochrome c. The lack of accumulation of apoiso-1-cytochrome c in cyc3 mutants, which contain CYCI mRNA, suggests that apoiso-1-cytochrome c is extensively regulated by a post-transcriptional process.The total complement of cytochrome c in derepressed cells of the yeast Saccharomyces cerevisiae is typically composed of 95% iso-1-cytochrome c and 5% iso-2-cytochrome c (1).Both iso-1-cytochrome c and iso-2-cytochrome c carry out identical or similar functions in mitochondrial electron transport (2). Iso-1-cytochrome c and iso-2-cytochrome c are encoded by the unlinked nuclear genes CYCJ and CYC7 (3-6), respectively, that are -=80% homologous in their DNA sequence (7) and that appear to be evolutionarily related (8). The biosynthesis of the two isocytochromes c, similar to the biosynthesis of other heme proteins, is decreased by growth in glucose media (catabolite repression) and by growth with anaerobic conditions (reviewed in ref.