Chemical sympathectomy is known to produce a denervation supersensitivity in smooth muscle in which responsiveness to adrenoceptor agonists is increased, resulting in increased agonist potency. This has long been assumed to be due to a general increase in the number of receptors on the smooth muscle. However, we have recently suggested that denervation results rather in an alteration in the proportion of differing subtypes of alpha-adrenoceptor (Cleary et al. 2004). In rat vas deferens, we found that sympathectomy (by i.p. injection of 6-hydroxydopamine) resulted in an increase in the proportion of alpha1D-adrenoceptors from undetectable to approximately 40% of the receptor population (the remainder being predominantly alpha1A-adrenoceptors). This increase in the number of alpha1D-adrenoceptors in ligand binding studies was matched by an increase in the potency of noradrenaline and an increase in the alpha1D-adrenoceptor mediated component of the contraction. In this study, we wished to examine whether this effect of sympathectomy can also be demonstrated in mouse vas deferens. In vas deferens from C57 Wild type mice, chemical sympathectomy increased the potency of noradrenaline at producing contractions as compared with vehicle treatment. Hence, denervation supersensitivity occurs in this preparation. However, alpha1A-adrenoceptor antagonism virtually abolished contractions in normal vas deferens, but not in denervated tissues, whereas alpha1D-adrenoceptor antagonism significantly reduced agonist contractions in denervated but not normal tissues. These results suggest that chemical sympathectomy results not in a general increase in the number of alpha-adrenoceptors, but rather in a change from alpha1A to alpha1D adrenoceptors. The increased sensitivity to noradrenaline is then caused not by an increase in number of receptors, but a change to alpha1D-adrenoceptors for which noradrenaline has high affinity.