Methapyrilene hydrochloride (MPHC), N-nitrosomethylaniline (NMA), N-nitrosomethyl-3-carboxypropylamine (NMCP) and N-nitrosodiethanolamine (NDELA) are reputed to be nonmutagenic carcinogens because they are genetically inactive in Salmonella mutagenesis tests but produce cancer in rats. We have assayed these compounds for their genetic activity with diploid strains D7, D7-144, and RMO52 of Saccharomyces cerevisiae. The compounds MPHC and NMA were highly toxic to the cells and induced gene conversion and reverse mutations in strains D7, D7-144 and RMO52. Metabolic activation was not required for this activity. However, in acidic (pH 5) medium, the genetic activity and cell toxicity of MPHC and NMA were markedly reduced. Ascorbic acid suppressed the mutagenicity and toxic effects of MPHC. Mutagenicity of NDELA was enhanced in strain D7-144 when cells were treated in acidic medium. At pH 7, NDELA was not mutagenic. NMCP induced reversed mutations in strains D7-144 and RMO52 in the absence of metabolic activation. Our results indicate that the four carcinogens, MPHC, NMA, NMCP and NDELA, require different physiological conditions for the expression of their genetic activity.