Possible hypertension-related alterations in the nature- and receptor reserve of the muscarinic (M) receptors mediating endothelium-dependent vasodilation remain to be elucidated. Therefore we used 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMPmustard), an irreversible M3-receptor antagonist, to estimate the receptor reserve for the methacholine (MCh)-induced endothelium-dependent vasodilation in perfused mesenteric vascular bed preparations obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats, respectively. The concentration-response curve parameters for the MCh-induced vasodilation were similar in both types of preparations. 4-DAMPmustard concentration-dependently decreased the maximal effect (Emax) of MCh without altering (N.S.) the pD2 in either type of preparation. The Emax was decreased to the same extent (N.S.) in both types of preparations. The dissociation constants of MCh for the response to muscarinic stimulation were comparable in preparations from SHR and WKY rats. The receptor reserve for this response, which is relatively low, does not appear to differ between vessels from SHR and WKY. It is concluded that an endothelial dysfunction does not seem to occur in perfused mesenteric resistance vessels from SHR. Also, the nature- and M-receptor reserves to not appear to differ. Therefore there are no important hypertension-related alterations in the M-receptor mediating endothelium-dependent vasodilation, at least in the experimental model used.