The gastric cytoprotective action of SU-88, an anti-ulcer agent, was studied in rats. SU-88 dose-dependently prevented the formation of gastric lesions induced by absolute ethanol as observed by PGE2. The efficacy of SU-88 when given i.p. was more potent than the p.o. administration. Indomethacin (5mg/kg, p.o.) given 30 min prior to SU-88 dosing blocked this protective effect, whereas it was not affected when indomethacin was given 30 min after the SU-88 dosing. Cimetidine, on the other hand, failed to exert a protective effect against the ethanol-induced lesions and caused a significant increase in the lesions induced by 0.6N HCI. Pretreatment with SU-88 prior to cimetidine resulted in a marked reduction in the lesions. SU-88 was found to increase the synthesis of gastric glycoproteins and to prevent the reduction of glycoprotein synthesis caused by the administration of absolute ethanol. However, no increase in the synthesis was observed 5 min after the SU-88 dosing, although the lesion was significantly suppressed at that time. These findings indicate that SU-88 possesses a cytoprotective effect and that this effect seems to be mediated by the increase in endogenous PG.