The effects of hyper- and hypotonic solutions on vascular smooth muscle were studied using helical strips from human umbilical arteries. Hypertonic solutions evoked a biphasic contraction that consisted of early and late contractions. Verapamil or Ca<sup>2+</sup>-free conditions inhibited early contraction induced by tonicity of 340-539 mosm/kg. Under these conditions, late contraction induced by 340-407 mosm/kg was inhibited, whereas contraction induced by 539 mosm/kg was not. Hypotonic solutions evoked a monophasic contraction. Verapamil or Ca<sup>2+</sup>-free conditions inhibited contraction induced by tonicity of 249-266 mosm/kg but not by tonicity of 213 mosm/kg. Hyper- or hypotonicity-induced contractions were not affected by the presence or absence of endothelium. These results suggest that a small increase or decrease in tonicity within the pathophysiological range of osmotic pressure (260–340 mosm/kg) evokes contraction in human umbilical arteries by stimulating calcium influx through voltage-sensitive Ca<sup>2+</sup> channels.