We divided 40 male Syrian golden hamsters into four groups of 10 animals each, and we treated both cheek pouches of each hamster three times a week as follows: group 1, 50 microL of sesame oil; group 2, 50 microL of 6% nicotine in sesame oil; group 3, 50 microL of 1% 7,12-dimethylbenz[a]anthracene (DMBA) in sesame oil; and group 4, 50 microL of 1% DMBA in 6% nicotine in sesame oil. Cheek pouches were examined clinically and histologically after 12 weeks of treatment. Hamsters treated with DMBA and nicotine showed significantly (P less than .001) more tumors and a significantly (P less than .05) greater-than-expected proportion of large tumors (greater than or equal to 3-mm diameter) than hamsters treated with DMBA alone. Histologically, there was a greater degree of dysplasia in lesions from the group receiving DMBA plus nicotine than in the DMBA only group. The results suggest that nicotine acts as a cofactor in DMBA tumorigenesis.