BACKGROUND Acute administration of prostaglandin E (PGE) may be cytoprotective for hepatocytes in acute hepatitis and for gastric mucosa in cirrhotic rats. We examined the effects of long-term PGE treatment on liver and stomach in cirrhotic rats. METHODS Cirrhosis was induced by bile duct ligation. Controls had a sham operation. Half the rats received a PGE1 analogue, misoprostol (PGE1) (10 micrograms orally, daily) on days 1-29 postsurgery, and the others received vehicle only. On day 31, all rats underwent ex vivo gastric chamber procedures. Liver chemistry, portal pressures, and hepatic and gastric tissue levels of prostaglandin E2, leukotriene B4, myeloperoxidase, and collagen were determined. RESULTS PGE1-treated cirrhotic rats had less hepatosplenomegaly, lower serum alanine aminotransferase levels, and portal pressures and higher arterial pressure than vehicle-treated cirrhotic rats. Hepatic and gastric leukotriene B4, myeloperoxidase and collagen levels were significantly lower in the PGE1-treated compared with vehicle-treated cirrhotic rats. Vehicle-treated cirrhotic rats had greater spontaneous and ethanol-induced gastric damage and failed to show a gastric hyperemic response to ethanol, whereas PGE1-pretreated rats did. PGE1 did not significantly affect sham-operated rats. CONCLUSIONS Long-term PGE1 administration was cytoprotective for both the liver and gastric mucosa in cirrhotic rats. Clinical trials of PGE in human cirrhosis or portal hypertensive gastropathy may be warranted.