Experiments were designed to determine the effect of 17 beta-estradiol on endothelium-dependent responses of isolated arteries. Ovariectomized female New Zealand rabbits were treated either with 17 beta-estradiol (100 micrograms i.m.) or with solvent for 4 days. After excision, femoral arteries were cut into rings and suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Rings from the 17 beta-estradiol-treated rabbits showed an enhanced endothelium-dependent relaxation to acetylcholine (3 x 10(-9)-3 x 10(-8) M) in the absence or presence of indomethacin. Under the same experimental conditions, the endothelium-dependent responses to the calcium ionophore A23187 were unchanged. In the absence of indomethacin, the response to adenosine diphosphate was depressed in rings with endothelium taken from animals treated with with 17 beta-estradiol; in the presence of the inhibitor of cyclooxygenase, the endothelium-dependent responses were comparable in blood vessels from treated and untreated rabbits. This study suggests that endothelium-dependent responses of arteries can be modulated by steroid hormones.