This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin.