We studied interactions of human platelets and neutrophils with particular reference to the arachidonic acid pathway. Suspensions of [3H]-arachidonate-labeled platelets and unlabeled neutrophils were stimulated with ionophore A23187. We detected several radioactive arachidonate metabolites, which are not produced by platelets alone. This included [3H]-labeled leukotriene B4 (LTB4), dihydroxyeicosatetraenoic acid (DHETE) and 5-hydroxyeicosatetraenoic acid (5-HETE). When the platelet product,[3H] 12-HETE, was added to ionophore-stimulated neutrophils, DHETE was formed. In addition, when [3H] 5-HETE, a neutrophil arachidonate product, was added to stimulated platelets, DHETE was the major metabolite. We, therefore, suggest that upon stimulation, the platelet derived arachidonate can serve as precursor for the neutrophil-derived eicosanoids LTB4 and 5-HETE and that the platelet-derived product 12-HETE can be metabolized to DHETE by stimulated human neutrophils. It would appear that the platelet and neutrophil lipoxygenase pathways take part in cell-cell interactions-an observation which suggests a role for the neutrophils which are present in hemostatic plugs, thrombi and inflammatory processes.