The vascular endothelium plays an important role in the regulation of vascular tone, by producing both vasodilating and vasoconstricting mediators. Using intravital videomicroscopy, this study examined the in vivo responses of the rat cremaster muscle microcirculation to topical application of endothelin-1 (ET-1), as well as the effect of verapamil pretreatment on these responses. ET-1 produced a potent and persistent vasoconstriction in arteries and veins which lasted for 150 min. The contractile response to ET-1 was significantly more prolonged in arterioles (11 to 30 microns) than in small arteries (40 to 70 microns). Pretreatment of the muscle with verapamil did not inhibit the initial vasoconstrictive action of ET-1, but produced a significant (p < 0.0001) reduction in the recovery time required for vessel relaxation in both small arteries and arterioles. The results suggest that Ca2+ channels contribute to the prolonged vasoconstriction induced in microvessels by ET-1. Because this prolonged vasoconstriction may be responsible for the "no-reflow" phenomenon which occurs in microsurgical procedures, therapy with a calcium antagonist may be useful in attenuating its duration.