The immunomodulator muramyl tripeptide-phosphatidylethanolamine (MTP-PE) has been shown to enhance host resistance against a variety of experimental infections and to cure influenza virus infection in mice when given in a single dose, even at a late stage of the disease. Tests of its capacity to induce alpha/beta- and gamma-interferon (IFN-alpha/beta and -gamma) in vitro demonstrated that it is neither an inducer nor a primer of IFN synthesis. On the contrary, we found that it inhibits the induction of IFN-alpha/beta and -gamma by poly(rI:rC), Newcastle disease virus, lipopolysaccharide, or concanavalin A in adherent cells from the peritoneal cavity and spleen of mice. The antiviral activity of already induced or exogenously added murine IFN was, however, not impaired.