As natural killer (NK) cell activity is an essential constituent of host defence systems and reactive oxygen intermediates participate in such defence, the effect of scavengers of oxygen radicals on NK cell activity was investigated. Hydroxyl radical (OH) scavengers (dimethyl sulphoxide (DMSO), thiourea, dimethylurea, tetramethylurea, benzoic acid, ethanol, methanol and ethylene glycol) inhibited NK cell activity. Catalase, a scavenger of H2O2, and superoxide dismutase (SOD), a scavenger of O-2, either alone or in combination, did not inhibit NK cell activity. Inhibition of the lipoxygenase pathway of arachidonic acid metabolism, a potential source of cellular OH, with nordihydroguaiaretic acid and 5,8,11,14-eicosatetraynoic acid (ETYA) resulted in marked inhibition of NK cell activity. Inhibition of the cyclooxygenase pathway with acetylsalicylic acid or indomethacin had minimal effects on NK cell activity. Taken together, these findings suggest that OH, possibly generated via the lipoxygenase pathway of arachidonic acid metabolism, is critical for NK cell cytotoxicity.