Contractile responses of rat vas deferens were studied with particular attention directed to the role of receptors and neuronal control. Marked contraction of the vas deferens was observed with alpha-adrenergic agonists, depending on their concentrations. This tissue had a low sensitivity to ACh. Four days after denervation, this tissue showed a supersensitivity to alpha-adrenergic agonists and a high K+ concentration, but not to ACh. The increase in sensitivity to alpha-agonists resulted in an enhancement of the maximal response and a shift of the concentration response curve to lower concentrations of these reagents. Alterations were seen in the alpha-adrenergic receptors in the rat vas deferens, assayed by measuring the binding of [3H]WB4101. The maximal binding sites decreased significantly to 86 from 142 fmoles per mg protein. The affinity of the receptors for alpha-agonist, determined by measuring the ability of agonists to displace bound [3H] WB4101, increased significantly, while the affinity to alpha-antagonists remained unchanged. Studies on [3H]QNB binding indicated no significant change in muscarinic ACh receptors after denervation. Thus, supersensitivity of the alpha-adrenergic mechanism mediated by a specific change in affinity of alpha-receptors occurs after denervation of rat vas deferens. These changes in sensitivity and in receptors are discussed in relation to the characteristics and roles of alpha-receptors in the rat vas deferens.