The mutagenic activity of propylene-oxide (75569) was tested in rats, mice, and Drosophila-melanogaster. Male rats and mice were exposed to either filtered air or propylene-oxide in exposure chambers for 7 hours per day on 5 consecutive days. Male rats were mated to virgin females post exposure, and mutagenicity was assessed by examination of the uterine contents in week two of gestation, according to the dominant lethal test. The male mice were sacrificed in post exposure weeks one, three, five, seven, and nine, and mutagenic activity assayed by the sperm head morphology test. Approximately 200 adult Drosophila males received a static 24 hour exposure to propylene-oxide prior to mating, and mutagenicity was determined by the sex linked recessive lethal assay. Mutagenic activity attributable to propylene-oxide was not detected by either the dominant lethal test or the sperm head morphology test. No abnormal forms were detected for either of the mammalian species. Exposure of male Drosophila to propylene-oxide resulted in a statistically significant increase in the number of dominant lethals occurring after mating of the F1 females. The differences in the results of the mutagenicity tests were discussed with regard to the reactivity of the polypropylene-oxide molecule, sample size, and maximally tolerated concentrations. The authors recommend continued caution with regard to potential human exposure, based on mutagenicity of propylene-oxide in Drosophila.