The relative antioxidant effect of ampicillin, ceftazidime, ceftriaxone, and cefuroxime on oxygen-reactive species was examined in vitro using stimulated human polymorphonuclear neutrophils. There was no evidence that any of the beta-lactam agents tested had an effect on superoxide or H2O2 generation. In contrast, all of the beta-lactam agents prevented hypochlorous acid (HOCI) chlorination of 1,1-dimethyl-4-chloro-3,5-cyclo-hexanedione in a cell-free system at concentrations of < 10 microg/ml. Furthermore, all antibiotics provided dose-dependent protection against HOCI cytotoxicity to 16HBE140 bronchial epithelial cells. Taken together, these data indicate a possible therapeutic role for beta-lactam agents in protecting host tissues from HOCI-induced oxidative damage.