We investigated the effects of several concentrations of extracellular ATP on the release of intracellular ATP by human umbilical vein endothelial cells (HUVEC) in primary cultures. When ATP is added to the medium of cultured EC at a concentration of 1 microM, it is readily degraded by extracellular enzymes; 10 microM ATP added to the culture medium provokes a transient but significant increase, followed by a decrease in the concentration of extracellular ATP. At a concentration of 100 microM, there was a significant release of ATP and its level was maintained in the culture medium throughout the experiment. Our results show that extracellular ATP leads to a sustained release of intracellular ATP by HUVEC. Such sustained self-perpetuating release of ATP is likely to play an important part in physiological and pathological local vascular control mechanisms.