To determine the impact of gastric hypoacidity and acidic beverages on delavirdine mesylate pharmacokinetics in HIV-infected subjects, matched subjects with (n = 11) and without (n = 10) gastric hypoacidity received delavirdine 400 mg tid with either water or an acidic beverage (usually orange juice). The pharmacokinetics of delavirdine and its N-desalkyl metabolite were determined over 8 hours after 14 days of each treatment. Gastric pH was measured at baseline and during each pharmacokinetic evaluation. Delavirdine exposure (Cmax, AUC0-->8 h, and Cmin) was approximately 50% lower and the extent of delavirdine metabolism was higher in subjects with gastric hypoacidity. Orange juice produced a lower mean gastric pH compared to water and increased delavirdine absorption by 50% to 70% in subjects with gastric hypoacidity. However, orange juice had a marginal impact on delavirdine exposure in subjects without gastric hypoacidity. HIV-infected subjects with gastric hypoacidity significantly malabsorb delavirdine. Delavirdine administration with acidic beverages improves, but dose not normalize, absorption in these subjects.