The relative antioxidant efficacy, in vitro, of several antibiotics was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNL) and the cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). Three tetracyclines (tetracycline HCl, oxytetracycline HCl, and minocycline HCl), erythromycin, cephalexin, penicillin G, chloramphenicol, and streptomycin were used as test drugs. At concentrations comparable to therapeutic blood levels, tetracycline HCl, oxytetracycline HCl, minocycline HCl, and erythromycin inhibited some of the ROS production by PMNL. In the xanthine-xanthine oxidase system, only minocycline HCl suppressed the H2O2 level. Cephalexin, penicillin G, chloramphenicol, and streptomycin did not affect any of the ROS examined at the concentrations tested. The capacity of some of these agents to inhibit ROS generation by PMNL may account, in part, for their efficacy in inflammatory skin diseases such as acne vulgaris. The antioxidant effect of these antibiotics does not stem from their capability to scavenge ROS, but originates rather from their effect on PMNL cell function directly with resultant anti-inflammatory effects on the inflammatory processes.