Enoxacin is a quinolone antibacterial agent currently being developed for oral and intravenous treatment of bacterial infections. Ten healthy subjects received a single 400-mg intravenous dose of enoxacin alone, with 300 mg (four times daily) oral cimetidine and with 150 mg (twice daily) oral ranitidine. Serial blood and urine samples were collected over a 48-hour period. Plasma and urine enoxacin concentrations were determined using a validated high-performance liquid chromatographic method. Mean enoxacin plasma concentrations were higher after administration of enoxacin with cimetidine than those measured after enoxacin alone or enoxacin with ranitidine. Cimetidine coadministration reduced enoxacin renal clearance by 26% and systemic clearance by 20%, and resulted in a 30% increase in elimination half-life. In contrast, concurrent ranitidine therapy did not significantly alter the pharmacokinetics of intravenous enoxacin.