We have characterized the ontogeny of gastric mucosal permeability responses to luminal H+ and investigated the effect of prostaglandins (PGs) on these responses in the neonate. Mucosal responses to instillation of HCl (100-600 mN) were measured in rats between 10 and 60 days after birth. Permeability changes were expressed as H+ loss and Na+, K+, and protein appearance in the luminal instillate. Responses to 100 and 200 mN HCl were low at all ages. Instillation of 300 or 400 mN HCl produced larger transmucosal fluxes of ions and protein in animals older than 20 days of age compared with younger animals. High concentrations of acid (500-600 mN HCl) produced large fluxes of ions and protein at every age examined. The responses in suckling animals were less than those seen in rats 25 days of age or older. In each age group mucosal HCO-3 secretion was inhibited by HCl concentrations greater than 100 mN. In each age group the mucosal response to 350 mN HCl was reduced by either 16,16-dimethyl-PGE2 (2 micrograms/kg ig) or a PGI2 analogue (Iloprost; 100 micrograms/kg ig). The effect of either prostanoid was greater in animals younger than 25 days of age compared with older rats. PGE2 and 6-keto-PGF1 alpha were detected in the gastric mucosa at all ages examined. Suckling animals had higher levels of either prostanoid. PGE2 levels decreased after 30 days, while levels of 6-keto-PGF1 alpha remained constant. These data suggest that 1) the susceptibility of H+-induced alterations in mucosal permeability to ions and protein increases as the animal ages, 2) the gastric mucosa of weanling rats is sensitive to PGs, and 3) PGE2 and 6-keto-PGF1 alpha are present in neonatal rat mucosa.