Epidermal growth factor (EGF) at physiologic concentrations (0.001-0.1 .mu.g/ml) stimulated the release of [14C] arachidonic acid [14C-AA] from pig epidermis. Although EGF stimulated the release of AA in the absence of exogenously added Ca to some extent, the addition of Ca (0.3-1.2 mM) significantly potentiated the release of AA stimulated by EGF. Ionophore A23187, which is known to stimulate phospholipase A2 activity by opening the Ca gates, potentiated the EGF-stimulated release of AA. The stimulatory effect of EGF was partially inhibited by the addition or mepacrine (70% inhibition at 10 .mu.M) and by the pretreatment of hydrocortisone (60% inhibition at 1.0 .mu.M). The loss of 14C-labeled phospholipids in pig epidermis was mainly due to the degradation of 14C-labeled phosphatidylcholine. EGF apparently stimulates phospholipase A2 activity and results in the increased release of AA.