The isolation and characterization of oncogenes from human colon cancer and the recognition of their homology with the ras gene of the Harvey and Kirsten strain of murine sarcoma virus (MSV) led us to investigate the effect of exogenous MSV on 1,2 dimethylhydrazine (DMH)-induced colon carcinoma in rats. DMH, 20 mg base/kg, was injected weekly for 10 weeks into Sprague-Dawley rats. The Moloney murine sarcoma virus (MSV-M) was injected (200 focus-forming units) intraperitoneally into 15 rats 48 hours after the last DMH injection or in 12 rats before the first DMH injection. Controls consisted of 12 rats receiving 10 injections of DMH only, nine rats receiving MSV-M alone, and 10 untreated rats. All tumors induced were adenocarcinomas of the gastrointestinal tract, characteristically induced by DMH and not by MSV-M. In the late virus group there was an augmentation of colon tumor induction (mean, 2.2 versus 1.1 colon tumors/rat, p less than 0.05), and in the MSV pretreated group, there was also significant augmentation of colon tumor induction (mean, 2.4 versus 1.1 colon tumors/rat, p less than 0.005) when compared with rats treated with DMH alone. Rats treated with MSV-M alone and untreated rats had no tumors. This is the first study to suggest the importance of exogenous viral infection in chemically induced colonic carcinogenesis.