The mechanism involved in the effects induced by the activation of perineural non-adrenergic non-cholinergic (NANC) nerves or by exogenous calcitonin gene-related peptide (CGRP) was investigated in the rat mesenteric vascular bed (MVB) perfused with Kreb's solution containing methoxamine and guanethidine. The activation of NANC terminals of the tissue was carried out by means of electrical field stimulation (EFS). An increase in the perfusion pressure of the preparations was observed in the presence of two inhibitors of nitric oxide synthase: NG-monomethyl-L-arginine (L-NMMA) (100 microM) and NG-nitro-L-arginine methyl ester (L-NAME) (100 microM). However L-NMMA and L-NAME did not modify the relaxant effect induced by EFS and exogenous CGRP. Furthermore the relaxant effect induced by EFS and exogenous CGRP was not affected by the removal of endothelium from the preparations. These results provide evidence that the vasodilation induced by NANC stimulation or by exogenous CGRP in MVB does not involve NO production.