The myeloproliferative disorders are characterized by frequent bleeding and thrombotic complications, which have been attributed to abnormal platelet function. In 24 of 60 patients studied, reduced activity of the platelet lipoxygenase pathway for oxygenation of arachidonic acid was revealed by a new direct assay. This assay measured arachidonic acid-induced oxygen consumption in platelets preincubated with aspirin to block cyclooxygenase activity. Patients with secondary polycythemia or thrombocytosis had normal lipoxygenase activity . In the cells of seven of eight patients with lipoxygenase deficiency arachidonic acid induced increased synthesis of thromboxane, the major cyclooxygenase product. Nevertheless, patients with deficient lipoxygenase activity tended to have episodes of hemorrhage rather than thrombosis. Bleeding complications occurred in 67 per cent of patients with lipoxygenase deficiency, but in only 19 per cent of those with normal lipoxygenase activity (P less than 0.001). In contrast, 13 per cent of lipoxygenase-deficient patients, but 31 per cent of patients with other myeloproliferative disorders, had thromboembolic complications. Measurement of platelet lipoxygenase activity may be of diagnostic value in distinguishing myeloproliferative disorders from secondary thrombocytosis or polycythemia. Lipoxygenase deficiency may prove to be a useful natural model for investigating the role of lipoxygenase products in hemostasis.