Arachidonate induces aggregation of human polymorphonuclear (PMN) and mononuclear (MNL) blood leukocytes. This is mediated by the lipoxygenase pathway, as it is prevented by lipoxygenase inhibitors and can also be induced by leukotriene B4 (LTB4). Vitamin E and vitamin C have profound effects on the functional state of leukocytes, some of which may involve the lipoxygenase pathway. This study shows that both vitamins inhibit arachidonate-induced aggregation of PMN and MNL, in a concentration-dependent way. BW-755, previously shown to inhibit arachidonate-induced PMN and NML aggregation, was found to potentiate the inhibitory activity of both vitamins. When LTB4 was used as an aggregating agent, vitamin E markedly inhibited PMN and MNL aggregation, whereas vitamin C was ineffective. The prevention of PMN and MNL aggregation by vitamin E might account, at least partially, for the reported beneficial effects of vitamin E supplementation in some experimental syndromes characterized by leukocyte activation.