Previous studies have suggested similarities between the effects of exogenously administered glucocorticoids and prostaglandins in the developing rat small intestine. In this study the effects of exogenously administered glucocorticoids and prostaglandins were compared. In addition, the effects of prostaglandins in adrenalectomized rats were evaluated. Members of both classes of compounds stimulate small intestinal disaccharidase activities, and increase RNA to DNA ratio and brush border membrane protein synthesis. Hydrocortisone accelerates enterocyte turnover, whereas prostacyclin does not. Enteral administration of 16,16-dimethyl prostaglandin E2 stimulates disaccharidase activities in intact as well as sham-operated and adrenalectomized animals. The data suggest that certain prostaglandins may play a role in small intestinal metabolism which is similar to that of the glucocorticoids but is independent of the adrenal-intestinal axis.