We found that DMSO protected hyaluronic acid against deploymerization due to either of two sources of .OH, gamma irradiation or activated PMN. These findings are consistent with previous studies in which DMSO blocked the effects of .OH in other test systems. Specifically, DMSO prevented depolymerization of hyaluronic acid by enzymatically generated oxygen radicals, presumably including .OH. Furthermore, DMSO inhibited the bactericidal activities of .OH generated either by the Fenton reaction or by activated PMN. Also, DMSO protects against radiation in vivo, presumably by scavenging .OH, as in the present in vitro studies. Finally, in yet another in vitro system, DMSO protected plasmid DNA against nicking by .OH generated by radiation. Protection of hyaluronic acid by DMSO against PMN-mediated depolymerization may have some clinical relevance. PMN, which release .OH, may contribute to breakdown of hyaluronic acid and connective tissues in some inflammatory conditions where influx of PMN is prominent, such as in arthritis. DMSO, or other antioxidants, might then decrease the injurious effects of PMN-released oxidants.