Low doses of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) have been shown to augment the salivary volume secretion evoked by muscarinic receptor agonists or substance P (SP) in rat parotid gland. Since VIP and CGRP are known to activate adenylate cyclase, we have studied whether forskolin, which directly activates this enzyme, can mimic the effects of these peptides on salivary secretion from the parotid gland in anaesthetized (Inactin 0.5 g kg-1 i.p.) rats. We have also studied the effect of the secretagogues and peptides on glandular blood flow as revealed by the laser Doppler technique. Carbachol (5 nmol kg-1) and SP (185 pmol kg-1) injected i.v. caused a transient increase in parotid blood flow and a decrease in systematic blood pressure concomitant with a salivary secretion of 3.3 +/- 0.3 mg (n = 22) and 18.7 +/- 1.9 mg (n = 25) respectively. VIP (150 pmol kg-1) and CGRP (25 pmol kg-1) also caused a transient increase in glandular blood flow concomitant with a decrease in systemic blood pressure, but no salivary secretion. The glandular blood flow increased by 166 +/- 5% and 43 +/- 11% for VIP and CGRP respectively. When carbachol was given 20 s after the injection of VIP or CGRP, the secretory response was increased by about 250% and 60% respectively. The adenylate cyclase stimulator forskolin (2.5 pmol kg-1) produced the same type of response regarding blood flow and systemic blood pressure as VIP and CGRP and potentiated the salivary secretion evoked by carbachol (5 nmol kg-1) by about 100%.(ABSTRACT TRUNCATED AT 250 WORDS)