Abstract Sparfloxacin, a fluoroquinolone with a broad antimicrobial spectrum and long elimination half-life, is indicated for the treatment of community-acquired pneumonia and acute bacterial exacerbations of chronic bronchitis in adult patients. The present study was undertaken to determine the effects of skim milk and a high-fat breakfast without milk on the single-dose pharmacokinetic characteristics of this antibiotic. The pharmacokinetics of a single 200-mg dose of sparfloxacin were assessed in a 3-way crossover study that included 23 healthy male volunteers who had fasted, had ingested 240 mL of skim milk, or had consumed a standard high-fat breakfast. The subjects' mean age and weight were 26.5 years and 73.2 kg, respectively; 17 were white, 5 Hispanic, and 1 black. Neither skim milk nor the high-fat breakfast had a statistically significant effect on sparfloxacin absorption, as reflected in the maximum plasma concentration (C max) and area under the plasma concentration-time curve (AUC). Ninety percent confidence limits for logarithmically transformed AUC from time zero to infinity and C max were within the 80% to 125% range, demonstrating that the rate and extent of sparfloxacin absorption with skim milk or a high-fat breakfast were not different from those under fasted conditions. As indicated by an increase in the time to C max from 3.6 to 5.4 hours, the high-fat breakfast slightly delayed the onset of sparfloxacin absorption. Skim milk and the high-fat breakfast did not significantly affect the elimination kinetics of sparfloxacin. Sparfloxacin was well tolerated in all 3 treatment groups. Despite the apparent delay in the onset of absorption, the bioavailability of sparfloxacin in the healthy male subjects in this study population was not affected by concomitant administration with skim milk or a high-fat meal. Accordingly, the results suggest that sparfloxacin can be administered without regard to the ingestion of milk or meals.