1 Rabbit hearts were perfused with a solution containing [14C]-arachidonic acid (AA) and various concentrations of nicotine (3 x 10(-8) to 3 x 10(-5) M). The venous effluent was collected and extracted for lipid acid material, which was subsequently subjected to thin layer radiochromatography. 2 Human platelets were incubated with nicotine (10(-8) to 10(-4) M), in the absence or presence of unlabelled AA. The amount of smooth muscle stimulating activity resulting from 30s of incubation was tested on a rabbit aortic strip. 3 In hearts perfused with [14C]-AA; nicotine induced a dose-related depression of the release of [14C]-6-keto-prostaglandin F1alpha, and a parallel increase of [14C]-prostaglandin E2. 4 Nicotine neither induced synthesis of thromboxane in human platelets, nor affected the platelet synthesis of thromboxane induced by AA. 5 It is suggested that nicotine affects the metabolism of prostaglandin endoperoxides in the heart by inhibiting their conversion to prostacyclin and facilitating, directly or indirectly, the formation of prostaglandin E2.