The availability of a potent inducer of interferon, the synthetic double-stranded RNA (poly I.poly C), prompted us to determine its possible prophylactic and/or therapeutic effect on virus-induced sarcomas of mice. When treatment was begun prior to virus inoculation and repeated on alternate days, the majority of NIH Swiss mice inoculated with Moloney or Friend pseudotypes of Moloney murine sarcoma virus failed to develop tumors. Other experiments suggested that repeated injections initiated even after the establishment of tumor nodules were also effective. Mice injected on the day of birth with poly I.poly C develop high titers of interferon. The evidence favors, but does not establish, the interpretation that the observed tumor inhibition is mediated through the induction of endogenous interferon. These experiments demonstrate that treatment with poly I.poly C is followed by a regression of established murine sarcoma infection in mice.