The effect of chronic ethanol consumption on the carcinogenicity of N'-nitrosopyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) in male Syrian golden hamsters has been investigated. Groups of hamsters were maintained on either ethanol-containing or control liquid diets for 4 weeks prior to and during carcinogen treatment. NPYR or NNN was administered to ethanol-consuming or control hamsters by i.p. injection over a 25-week period in total doses of either 1 or 2 mmol. In the group treated with 1 mmol of NPYR and maintained on a control diet, we observed 1 of 20 hamsters with a nasal cavity tumor and 4 of 20 hamsters with tracheal tumors. In the group treated with 1 mmol of NPYR and maintained on the ethanol-containing diet, we observed 8 of 18 hamsters with nasal cavity tumors and 9 of 18 hamsters with tracheal tumors. The corresponding results in hamsters given 2 mmol of NPYR were: nasal cavity tumors, 14 of 21 (control) and 16 of 17 (ethanol); tracheal tumors, 8 of 21 (control) and 11 of 17 (ethanol). These results demonstrate that the carcinogenicity of NPYR is enhanced in ethanol-treated Syrian golden hamsters, particularly at the lower dose. In the groups treated with 1 mmol of NN and a control diet, we observed 1 of 21 hamsters with a nasal cavity tumor and 4 of 21 with tracheal tumors. In the corresponding ethanol-treated groups, we observed 1 of 17 hamsters with a nasal tumor and 5 of 17 with tracheal tumors. In the hamsters given 2 mmol of NNN, the results were: nasal cavity tumors, 5 of 21 (control) and 4 of 21 (ethanol); tracheal tumors, 9 of 21 (control) and 7 of 21 (ethanol). Thus, the carcinogenicity of NNN in the Syrian golden hamster was not affected by ethanol treatment. These results suggest that the metabolic activation of NPYR, but not that of NNN, may be enhanced by chronic ethanol consumption in the Syrian golden hamster.