Intraarticular injection of interferon inducer, double-stranded polyinosinate-polycytidylate (Poly I . C) caused acute synovitis in rats. This acute inflammatory response was accompanied by an increased concentration of prostaglandin E (PGE) in the synovial tissue. Double-stranded polyadenylate-polyuridylate (Poly A . Poly U) was less potent than Poly I . Poly C in inducing synovitis and increasing PGE concentration, while single-stranded polyinosinate (Poly I) or polycytidylate (Poly C) were inactive in these respects. Intraarticular injection of partially purified mouse fibroblast interferon also induced synovial inflammation. The present results suggest that interferon may be a mediator of viral inflammatory responses.