Sialic acids are negatively charged groups in the carbohydrate side chains of glycolipids and glycoproteins which line the external membrane surface. The goal of this study was to characterize the effect of neuraminidase, which selectively cleaves sialic acids, on contractile activity in vascular smooth muscle. Helically cut strips of rat tail artery were mounted in an organ chamber and isometric contractions were recorded. Following treatment with neuraminidase (0.2 U/ml, 1 h), contractile responses to norepinephrine were significantly greater than control responses. Phasic contractions to norepinephrine in calcium-free medium were not altered by neuraminidase, whereas following calcium depletion with EGTA, contractile responses to added calcium were greater in enzyme-treated strips than in control when activated with norepinephrine. The augmentation of norepinephrine-induced contractions following neuraminidase treatment was reversed by incubation of the arterial strips with N-acetylneuraminic acid (10<sup>-4</sup> M). Neuraminidase had no effect on contractile responses to potassium chloride, angiotensin II, and caffeine. Biochemical assay indicated that approximately 63% of the total sialic acid residues were removed from the arterial strips during incubation with the enzyme. It is concluded that a component for the control of the transmembrane calcium movement in response to norepinephrine is dependent on the presence of sialic acid residues.