L-929 cells injected s.c. into athymic nude mice cause the formation of single well-defined tumors at the site of inoculation. The development of these tumors is markedly inhibited by polyriboinsinic acid-polyribocytidylic acid [poly(l)-poly(C)], whether poly(l)-poly(C) treatment is initiated one day after L-cell inoculation or 3 weeks later, when tumors have grown to an appreciable size. The antitumor effect of poly(l)-ploy(C) was found to be dose dependent. Multiple injections of 100 microng poly(l)-poly(C) per mouse (congruent to 5 mg/kg) almost completely arrested tumor growth, but even at 1microng/mouse (congruent to 50 microng/kg), poly(l)-poly(C) caused a partial reduction in tumor growth. Mouse interferon administered exogenously in amounts that closely mimicked the interferon blood levels induced endogenously by poly(l)-poly(C) failed to duplicate the antitumor effects of poly(l)-poly(C). Hence, the role of interferon induction in the mechanism of antitumor action of poly(l)-poly(C) can be eliminated. Since all results were obtained with the use of athymic nude mice, the role of thymus-dependent immunity can also be eliminated. At the dosage regimens used to determine the inhibitory effect on L-cell tumor growth, neither poly(L)-poly(C) nor interferon altered the life-span of the nude mice.