OBJECTIVE The efficacy of omeprazole administered by the nasogastric route has not been adequately studied. We sought to determine whether nasogastrically administered omeprazole could effectively maintain an intragastric pH greater than 4.0 in patients hospitalized in a medical intensive care unit. METHODS Patients were considered eligible for the study if they had a nasogastric feeding tube in place and had not received omeprazole, antacids, or histamine-2 blockers in the 5 days preceding study enrollment. Exclusionary criteria included active GI bleeding or a mean baseline gastric pH greater than 4.0. Patients served as their own controls during a 24-h lead-in period, during which baseline intragastric pH was measured by gastric aspirate. Omeprazole, 20 or 40 mg, was administered once daily with water through a nasogastric tube. Intragastric pH was measured every 4-8 h for a maximum of 3 days following drug administration. RESULTS Twenty patients were considered eligible for the study; 10 were excluded because of an elevated baseline gastric pH (n = 8) or because proper gastric aspirates could not be obtained (n = 2). The mean baseline intragastric pH in four patients receiving omeprazole 20 mg q.d. was 2.4 +/- 1.1 and increased to 3.7 +/- 1.6 after drug administration (p = 0.013). The mean baseline intragastric pH in six patients receiving omeprazole 40 mg q.d. was 2.8 +/- 0.8 and increased to 5.7 +/- 1.1 after drug administration (p < 0.001). The percentage of intragastric pH values greater than 4.0 after drug administration was 34.2% in patients receiving omeprazole 20 mg q.d. and 84.7% in those receiving omeprazole 40 mg q.d. CONCLUSIONS Nasogastric omeprazole 40 mg q.d. is effective in maintaining an intragastric pH greater than 4.0 in critically ill patients. The nasogastric administration of omeprazole offers a cost-effective therapeutic option for acid suppression in patients at risk for stress mucosal ulceration.