The pharmacokinetics, safety, and disposition of the new antimicrobial fluoroquinolone ofloxacin were evaluated after oral administration in 14 healthy, male volunteers in a double-blind, placebo-controlled study. Ofloxacin was administered as 100-, 300-, and 600-mg doses separated by 1 week. Plasma and urine concentrations after each administration were measured using a sensitive and specific high-performance liquid chromatographic procedure. The distribution of ofloxacin was modeled using a two-compartment open-body model with first-order absorption. Maximum plasma concentrations and area under the plasma concentration versus time curve increased in a linear, dose-proportional manner over the range studied. At all levels, within 36 hours after administration, approximately 70% of the dose was recovered in urine as unchanged ofloxacin and only minimal amounts (less than 4%) as metabolites. No significant changes in the distribution or elimination of the compound were found over the 6-fold dose range. No major laboratory toxicities or clinically significant adverse effects were noted in either the ofloxacin or placebo group.