The effect of long-term misoprostol - a synthetic prostaglandin E1 analogue - ingestion on rat gastric morphology and cell turnover was studied. Misoprostol in a daily dose of 90 micrograms/kg or 9,000 micrograms/kg was intragastrically administered to rats. Control rats were treated with the vehicle only. Following 90 days of treatment, 3H thymidine was injected i.v. and rats were sacrificed 1 h later. Tissue sections were prepared from the stomach body and subjected to autoradiography. Misoprostol treatment significantly reduced body weight gain. High dose misoprostol treatment induced significant increases in gastric wall thickness and in gastric gland length. On the other hand, the labelling index was significantly reduced by treatment with high dose misoprostol. These results indicate that chronic administration of misoprostol in high doses increases gastric wall thickness and decreases gastric cell turnover, suggesting that administration of prostanoids causes an increase in cell survival and a decrease in cell shedding.