Repeated administration of indomethacin markedly delays spontaneous healing of experimental gastric ulcers induced in rats. To elucidate the underlying mechanism, the effect of indomethacin on the gastric mucosal blood flow around ulcers was examined. Gastric ulcers were induced 5 days after submucosal injection of an acetic acid solution into the stomachs of rats. Blood flow was determined by the hydrogen gas clearance method. The blood flow around ulcers was significantly higher than that in rats without ulcers up to 2 weeks after ulceration but had returned to within the normal range 3 or 4 weeks later. Indomethacin, administered SC at 1 mg/kg once or repeatedly for 1-4 weeks, had little or no effect on the blood flow in normal rats. However, such treatment significantly reduced the blood flow by 20%-30% of the corresponding control levels in rats with ulcers. Prostaglandin E2, administered SC at 3 mg/kg once, markedly prevented the reduction in the blood flow due to indomethacin. The administration of prostaglandin E2, with indomethacin for 4 weeks resulted in a significantly higher blood-flow level than the control and prevented the delay in ulcer healing. Omeprazole, administered SC at 30 mg/kg once or repeatedly with indomethacin for 4 weeks, had an insignificant effect on the blood flow around ulcers but prevented the delay in ulcer healing. In conclusion, the delayed ulcer healing caused by indomethacin might be partly related to the reduced blood flow around the ulcers.