1. The effects of rat calcitonin gene-related peptide (rCGRP), rat calcitonin (rCT) and salmon calcitonin (sCT) on the substance P-mediated (SP-mediated) secretion of fluid from the rat submandibular gland were investigated. 2. Rat CORP potentiated and prolonged the SP-mediated secretion of fluid from the rat submandibular gland in a dose-dependent manner. CGRP also enhanced methacholine-and phenylephrine-mediated secretion of fluid. 3. The potentiating effect of the combination of rCGRP and SP was somewhat reduced by pretreatment with spantide, human CGRP(8.37) and atropine but not by pretreatment with phentolamine or with propranolol. 4. Salmon CT at a low dose mimicked the effect of rCGRP on the SP mediated secretion of fluid, but its potency was lower than that of rCGRP. However, rCT had no effect on the SP-mediated secretion of fluid. 5. These results suggest that the potentiating effects of rCGRP and SP might involve cholinergic receptors, as well as CGRP and tachykinin receptors, and that sCT, but not rCT, is able to mimic rCGRP in potentiating the secretion of fluid induced by SP. (C) 1998 Elsevier Science Inc.