Endothelial cells in culture can modulate platelet aggregation and vascular tone, in part by producing prostacyclin (PGI2), a powerful vasodilator and inhibitor of platelet aggregation, but also by their ecto-ADPase activity, which initiates the conversion of pro-aggregating ADP to adenosine, a potent vasodilator and platelet inhibitor. We have now demonstrated that cultured aortic endothelial cells exposed to trypsin, thrombin or other stimuli can liberate a high proportion of their adenine nucleotides without substantial loss of lactate dehydrogenase. ADP rapidly accumulates extracellularly, reaching biologically active concentrations before there is further breakdown to adenosine. Whether this selective release of nucleotides is a response to damage, or whether it represents a specific secretory mechanism remains to be resolved. Cultured aortic smooth muscle cells can secrete adenine nucleotides in a similar manner, but extracellular conversion to adenosine occurs much faster.