Stumptailed macaques received a single i.v. dose of 14C-nicotine (5 microCi and 300 micrograms/kg) on several separate occasions to establish baselines. Then they were pretreated with phenobarbital (2.0 mg/kg/day im for 7 days) and 8 weeks later pretreated with cimetidine (8.5 mg/kg/day im for 4 days). Nicotine in the same dose as before was readministered after each pretreatment. The baseline pattern of nicotine metabolism observed in plasma and urine, highly reproducible within and between macaques, closely resembled that previously reported in humans using GC and HPLC analysis. In urine, nicotine and eight metabolites were identified, including high concentrations of metabolites A and G. Recently discovered in humans, metabolites A and G are of special interest for their long duration in the body. Phenobarbital pretreatment accelerated rates of production of all nicotine metabolites except nornicotine and nicotine-1'-N-oxide, whereas cimetidine retarded rates of production of five metabolites. Sex differences in nicotine metabolism resembled those reported in humans. Collectively, these results suggest that the stumptailed macaque may be a useful model for certain aspects of nicotine metabolism in humans.