This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection.