Recommendations that can be made to decrease the incidence of untoward NSAID-induced GI events include identification of the high-risk patient (Table 3). If it is important to treat these high-risk patients with NSAIDs, either the lowest possible dose of the NSAID, an alternative non-NSAID analgesic, or the nonacetylated salicylates should be used. If that is impossible and a nonsalicylate NSAID is required in the high-risk patient, one should treat concomitantly with tolerable doses of misoprostol and prescribe that the NSAID be taken with food. If the patient is intolerant of misoprostol, H2 antagonists or omeprazole should be considered to decrease the risk of developing an NSAID-induced duodenal ulcer. If patients are not in the defined high-risk groups, given the present costs of H2 antagonists, omeprazole, and misoprostol, there seems to be little justification in treating the patient prophylactically. However, if the patient develops progressive iron-deficiency anemia or occult fecal blood loss not due to an obvious malignancy, endoscopy can be recommended to determine the cause. If there is evidence of a significant NSAID-induced gastric or duodenal ulcer, the NSAID should be stopped and the ulcer treated. If that is impossible, the NSAID dosage should be as low as possible, and the ulcer treated. If an ulcer is found, either a biopsy for H. pylori or a serum assay for the organism should be obtained. Once the ulcer is healed through appropriate therapy, and if NSAIDs are still to be used, prophylaxis with misoprostol should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)