The production of prostaglandins by amnion is a key factor in the mechanism of human parturition yet the regulation of prostaglandin biosynthesis in amnion is poorly understood. Hence, we have investigated the regulation of epidermal growth factor (EGF) stimulation of prostaglandin biosynthesis in human amnion cells. This stimulatory action is inhibited by cycloheximide or actinomycin D at high concentrations, but enhanced at much lower concentrations of these protein synthesis inhibitors. An amnion-produced prostaglandin inhibitor or immediate early gene action may explain these effects. Pretreatment with phorbol esters (inhibition of protein kinase C activity) reduces basal prostaglandin production and attenuates the stimulatory action of EGF on prostaglandin biosynthesis. Hence, amnion prostaglandin biosynthesis is dependent partly on protein kinase C activity.