The direct effects of exogenous and endogenous prostaglandins (PGs) on damage to isolated gastric cells caused by ethanol were assessed in rats. 16,16-Dimethyl-PGE2 (dmPGE2) significantly inhibited cellular damage caused by 15% ethanol in three fractions rich in surface epithelial cells, rich in parietal cells, and rich in chief cells at the concentration of 10(-6) M but it was less effective either at a lower concentration (10(-7) M) or a higher concentration (10(-5) M). The surface epithelial cells synthesized 6-keto-PGF1 alpha and thromboxane (TX) B2 predominantly, and less PGE2. Indomethacin completely inhibited synthesis of these prostanoids. This agent induced cellular damage in a dose-related way and this damage was inhibited by 10(-6) M dmPGE2. Indomethacin alone at the dose of 10(-4) M, at which synthesis of prostanoids was completely inhibited, did not affect the viability of the cells, but made the cells susceptible to damage caused by 15% ethanol. This effect of a minimum dose of indomethacin was inhibited by 10(-6) M dmPGE2. These results suggest that dmPGE2 has a direct protective effect on the isolated gastric cells in rats, and this effect is not limited to a specific cell type. That endogenous prostanoids have a possible role in the maintenance of cellular integrity is also postulated.