The hypolipidemic agent nafenopin, (NF), has been reported to be carcinogenic to rat liver. To determine whether nafenopin exerts a promoting or syncarcinogenic effect in rat liver, its effect on liver carcinogenesis induced by N-2-fluorenylacetamide (FAA) was studied. In two separate experiments, male F344 rats were fed 0.02% FAA for either 10 or 8 weeks to induce preneoplastic liver lesions. Following a recovery period of 1 week, rats were given 0.01 or 0.02% NF in the diet for 23 weeks in one experiment and 0.05 or 0.1% for 24 weeks in the other. The final incidence of neoplasms, and their numbers, size distribution, and degrees of differentiation were not significantly different in groups given NF after FAA compared to those maintained on a basal diet after FAA. In the group treated with the highest dose level of NF following FAA, however, there was a decrease in the number of grossly visible small neoplasms. In contrast, the liver neoplasm promoter phenobarbital increased the multiplicity, although not the incidence, of liver neoplasms when given after FAA. Thus, four different dose levels of NF showed no promoting or syncarcinogenic effect on FAA-induced hepatocarcinogenesis.