The role of endothelium in isoprenaline-induced relaxation was investigated in aortic rings brought to different levels of pre-contraction. Relaxation elicited by isoprenaline decreased with increasing pre-contraction. However, relaxation was identical in rings with and without endothelium brought to the same initial tension by adjusting the noradrenaline concentration. Furthermore, isoprenaline increased cAMP and cGMP contents to the same levels whether endothelium was present or not. These results do not support an obligatory role for the endothelium in isoprenaline-induced relaxation in rat aorta. They indicate that relaxation induced by isoprenaline can be enhanced by the endothelium as a consequence of its effect on the precontraction level of the aorta.