Quantitative assays for the morphological transformation of 3T3 Swiss mouse cells by herpes simplex type 2 virus (HSV-2) were employed to examine the effect on cell transformation of chemical carcinogens and pro-carcinogens. The carcinogens tested were N-methyl-N'-nitro-N-nitrosoguanidine, quinacrine mustard, N-nitrosomethyl urea, urethane, and benzene. The pro-carcinogens tested were N-nitrosodimethylamine, 3-methylcholanthrene, benzo[a]pyrene, and p-dimethylaminoazobenzene. Exposure of the cells to the chemical compound and to the virus resulted in enhancement of transformation when compared to that observed with chemical or virus alone. Enhancement of transformation occurred in cells treated with all of these compounds. In general, enhancement occurred regardless of whether the cells were pre-exposed to the carcinogen or pre-infected with virus. These results are suggestive of combined herpes virus and chemical effects on cells resulting in increased risk of oncogenic transformation.