The interferon‐inducer, polyinosinate. Polycyctidylate [Poly (I). Poly (C)] stimulated both prostaglandin E (PGE) and hyaluronic acid (HA) production by human cultured synovial fibroblasts. Increased accumulation of PGE in the medium was noted within 3 hours of culture, while accumulation of HA was observed only after a 24 hour lag period. The stimulation of PGE and HA production by Poly (I) Poly (C) was prevented by aspirin and indomethacin. Human interferon was also effective in stimulating both PGE and HA production. Concomitant addition of cortisol to culture medium abrogated the stimulatory effect of Poly (I). Poly (C) and interferon on both PGE and HA production. Exogenous PGE2, however, overcame the inhibitory effect of cortisol on HA production. The present results suggest that the stimulatory effect of both interferon and Poly (I). Poly (C) on HA production may be mediated by PGE. Prostaglandins may thus play a role in the inflammatory process associated with viral infections.