The action of dipyridamole on the vascular production of prostacyclin (PGI2) has been investigated. Dipyridamole (1-100 microM) did not induce a significant stimulation of PGI2 release in any of the following experimental models: rings of rabbit aorta, cultured endothelial cells from bovine aorta or human umbilical vein, cultured explants of bovine aortic smooth muscle. The activity of known stimuli of PGI2 release (ADP, suloctidil, serotonin) and the capacity of dipyridamole to inhibit adenosine uptake into endothelial cells were carefully checked. Pretreatment of the rabbit aorta with dipyridamole (10-100 microM) prolonged the transient stimulation of PGI2 release induced by mechanical deendothelialization: this effect was probably due to a partial protection of the cyclooxygenase against oxidative self-inactivation. Our largely negative results are consistent with the current theory that the antiplatelet action of dipyridamole is mediated by adenosine and not by PGI2.