We studied the effects of various agents on prednisolone-induced gastric lesions in rats. Gastric lesions were produced by subcutaneous administration of 50 mg/kg of prednisolone once daily for 4 days to non-fasted rats. Daily oral administration of antipeptic, antisecretory agents and 16-dmPGE2 significantly inhibited the lesions. Antacids and PGI2 had little or not effect. These results suggest that the concomitant use of the above agents with steroid therapy to provide protection of the gastric mucosa warrants further attention.