Human blood platelet aggregation and the formation of icosanoids were studied in response to triethyl lead chloride (Et3PbCl). Concentrations higher than 75 μM stimulate platelets to aggregate, whereas low concentrations (≦ 20 μM) caused platelet hypersensitivity to aggregating agents such as collagen or arachidonic acid. Incubation of suspensions of washed platelets with Et3PbCl resulted in a stimulated liberation and subsequent metabolism of arachidonic acid. This response was dependent on the concentration of Et3PbCl and the incubation time. Using low concentrations of Et3PbCl and up to 3 h of incubation, the lipoxygenase product 12-hydroxy-5,8,10,14-icosatetraenoic acid was the major metabolite. Under normal conditions, however, stimulation of platelets with collagen, thrombin, or arachidonic acid leads to higher amounts of the cyclooxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid and thromboxane B2.The aggregation of human platelets induced by Et3PbCl was inhibited by three different drugs: acetylsalicylic acid, forskolin and quinacrine; but only quinacrine could prevent the liberation of arachidonic acid and the appearance of its metabolites. These specific effects of the inhibitors on Et3PbCl-stimulated platelets as well as the differences in the pattern of arachidonic acid metabolites and phosphatidic acid suggest a direct stimulatory action of Et3PbCl on platelet phospholipase A2.