Regional blood flow in the gastrointestinal tract (forestomach, corpus, antrum, duodenum, jejunum, and colon) was determined in the conscious rat by means of the microsphere technique. The effects on blood flow were determined after omeprazole (orally and intravenously) and cimetidine (intravenously) during both basal and pentagastrin-stimulated gastric acid secretion. Under basal conditions neither omeprazole nor cimetidine decreased the blood flow in the gastrointestinal tract in spite of pronounced inhibition of acid secretion. On the contrary, there was a tendency towards an increased blood flow in the mucosal layer of the corpus after the oral (80 mumol/kg) and the high intravenous (10 mumol/kg) dose of omeprazole. When omeprazole was given intravenously to rats during pentagastrin-stimulated acid secretion, blood flow in the gastric mucosa was unaffected in spite of complete or almost complete inhibition of acid secretion. In contrast, cimetidine decreased the mucosal blood flow, indicating that the pentagastrin-induced increase in blood flow to some extent is mediated by H2 receptors.