Peroxynitrite, formed by reaction of superoxide and nitric oxide, appears to be an important tissue damaging species generated at sites of inflammation. In this paper, we compare the abilities of several antibiotics to protect against peroxynitrite-dependent inactivation of alpha1-antiproteinase, and to inhibit tyrosine nitration by peroxynitrite, in vitro. Tetracycline, minocycline, doxycycline, rifamycin and rifampicin were highly protective in both assay systems, whereas several other antibiotics tested were not. The possibility that antibiotics could affect tissue injury at sites of inflammation by scavenging peroxynitrite is discussed.