AIDS patients may have achlorhydria, a condition that could result in drug malabsorption, especially of antifungals. The effect of a reduction in the production of gastric acid on the pharmacokinetics of the antimycotic fluconazole after a single 100 mg dose was investigated in a randomized two-way crossover study with 12 healthy volunteers. Gastric acid production was reduced by pretreatment with 20 mg omeprazole/day over a period of 7 days; pH and gastric emptying times were measured by a radiotelemetering pH capsule. Omeprazole pretreatment significantly raised the median gastric pH (from pH 1.1 to pH 4.7, p < 0.0001), but had no significant influence on gastric emptying time of the pH capsule (median = 4.3 vs 4.9 hours). The pharmacokinetics of fluconazole were unchanged; plasma parameters were Cmax = 2.04 micrograms/ml, tmax = 4.08 h and AUC = 98.91 h micrograms/ml after the omeprazole treatment, compared to 2.06 microliters/ml, 3.92 hours and 97.29 h micrograms/ml, respectively. The median bioavailability ratio of fluconazole before and after omeprazole treatment was 1.00. It is inferred that there is no interference of omeprazole with the plasma pharmacokinetics of fluconazole. The findings suggest that changes in gastric pH, as in patients with AIDS or those being treated with anti-ulcer drugs, should not influence the pharmacokinetics of fluconazole.