Available data suggest that: (1) the greater uptake of isoprene in mice relative to rats may not contribute to differences in sensitivity because the blood levels of total metabolites are similar in the two species; (2) in rats, saturation of blood levels of isoprene monoxide and the hydrocarbon could not be demonstrated at inhaled isoprene concentrations up to 8200 ppm, but saturation of blood levels of diols/diepoxide and of non-volatile metabolites occurred at approximately 1480 ppm (similar data are not reported for mice); (3) reaction of reactive isoprene metabolites with blood components in mice and rats is similar to reaction of butadiene metabolites in rats and much greater than that of butadiene metabolites in mice. This may contribute to the greater sensitivity of mice to butadiene carcinogenicity relative to isoprene carcinogenicity; (4) reported data do not conclusively show that differences in tissue concentrations of isoprene metabolites contribute to the differences in the relative potencies of isoprene and butadiene in mice or to the greater carcinogenic potency of isoprene in mice relative to that in rats.