Five different dose levels of 2‐acetylaminofluorene (2‐AAF) were fed to weanling mice of 4 different genotypes from three unrelated F1hybrids for 13 wk to determine differences in susceptibility to induction of bladder hyperplasia. Differences in the prevalence of hyperplasia per se and in the average grade of hyperplasia were interpreted as indicating greater susceptibility. On this basis, males of all genotypes were more susceptible than females. Among the genotypes, (AEXYS)F1mice (AY) were most susceptible, followed closely by yellowAvy/A(BALB/cXVY)F1mice (CV). Agouti Ali(BALB/cXVY)F1mice were less susceptible than their yellow siblings and similar to the (C57BL/6XC3H)F1mice. Neither body weight gain nor any of the biochemical parameters measured appeared to be affected at any dose level of 2‐AAF. However, quantitative differences in several biochemical characteristics were detected among the genotypes. Serum ?‐glutamyl transpeptidase activity was higher in the A Y mice than in the other hybrids. Among the CV mice, the yellow animals had lower glutathione S‐transferase (GST) activity than their agouti siblings. Hepatic GST activity was lower in CV mice than in either of the other hybrids. Hepatic cytochrome P‐450 and bsactivities were similar in all hybrids.