Acid-reducing drugs can cause increased growth of microbes, including fungus, because of high gastric pH. Our purpose was to evaluate the occurrence of mycotic infection in patients with duodenal ulcer on anti-ulcer therapy and to compare the effects of cimetidine, famotidine, and omeprazole. Eighty patients with duodenal ulcer (62 males and 18 female patients, 16-65 years old) were evaluated for mycotic infection before and after 6 weeks of therapy (cimetidine, 20 patients; famotidine, 40 patients; omeprazole, 20 patients). Mycotic infection was diagnosed by endoscopic biopsy from the ulcer edge subjected to smear, culture, and histopathology and by endoscopic brush samples and gastric aspirate. On the basis of these studies, patients were categorized as having no fungal growth, saprophytic growth, or significant fungal growth. Thirty-five (43.8%) patients had evidence of fungus before ulcer therapy, and 16 of the 35 (20%) had significant fungal growth. The fungal isolation rate was higher in older patients (> and = 45 years of age) and in those with an ulcer size > and = 2 cm. While there was no significant increase in the total number of patients with evidence of fungus after therapy (n = 36), there was a significant increase in those with significant growth (n = 27, p < 0.05) compared with pretreatment status. We found that posttreatment gastric pH of > and = 4 was associated with a higher fungal positivity rate (59.4%) than pH values < 4 (32.4%, p < 0.05). However, neither the type of drug used nor the response in terms of ulcer healing correlated with the presence of fungus. Regardless of the type of drug used, acid-reducing therapy is associated with increased significant fungal growth.