Secretion of gallbladder mucin is an important step in gallstone pathogenesis. Previous studies have demonstrated that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and prevent gallstone formation in animal models of cholesterol gallstone disease. The present study was performed to determine if chronic NSAID use was associated with a reduction in the mucin content or affected the lipid components of human gallbladder bile. Four groups of patients were identified retrospectively from a cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The index group consisted of 18 patients who were found to have gallstones at gastric bypass surgery and had a history of chronic NSAID use. Three other patient groups were identified from the cohort by matching this index population for sex, race, and age according to the following criteria: (1) patients with gallstones who had not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use, and (3) patients without gallstones and without a history of NSAID use. Gallbladder bile was obtained from all patients by direct aspiration from the gallbladder at the time of surgery. Patients with gallstones had a significantly (P < 0.02) greater concentration of gallbladder mucin in their gallbladder bile compared to patients without gallstones (0.897 +/- 0.226 vs 0.173 +/- 0.039 mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients with a history of chronic NSAID use (1.18 +/- 0.43 vs 0.74 +/- 0.19 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)