Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.