The early stages of N-2-fluorenylacetamide [(2-FAA) CAS: 59-96-3]-induced liver carcinogenesis in inbred F344 male and female rats and the effect of gonadectomy on liver carcinogen biotransformation capability and hepatocarcinogenesis were studied. Feeding of 2-FAA induced more altered hepatocellular foci characterized by exclusion of cellular iron and gamma-glutamyl-transferase activity in male rats than in female rats. At 6-22 weeks after cessation of carcinogen exposure, only males developed liver neoplastic nodules. Liver cytochrome P450, aryl hydrocarbon hydroxylase, and uridine-5'-diphosphateglucuronosyltransferase activity toward p-nitrophenol, but not phenolphthalein, were greater in males than in females. Gonadectomy of males reduced the activities that were greater than in females, whereas none was significantly altered by gonadectomy of females. Gonadectomy of male rats prior to 2-FAA feeding suppressed the induction of both altered foci and neoplastic nodules, whereas in female rats gonadectomy prior to 2-FAA feeding enhanced the induction of foci. Gonadectomy of males after administration of 2-FAA slightly enhanced the persistence of foci at 6 and 12 weeks after removal of carcinogen, but it did not affect their persistence by 22 weeks post carcinogen or the incidence of neoplastic nodules. However, only the males that were gonadectomized after receiving 2-FAA developed hepatocellular carcinomas at 22 weeks. Gonadectomy of females after receiving 2-FAA did not affect the persistence of foci, and no liver neoplasms developed. Thus gonadectomy of male rats, which reduced liver carcinogen metabolism, when done before carcinogen feeding had the greatest effect on hepatocarcinogenesis.