The role of K+ and Cl channels in salivary secretion was investigated, with emphasis on the potential role of Ca2+-activated K+ channels. Ligand saturation kinetic assays and autoradiography showed large-conductance (BK) K+ channels to be highly expressed in rat submandibular and parotid glands, whereas low-conductance (SK) K+ channels could not be detected. To investigate the role of K+ and Cl channels in secretion, intact rabbit submandibular glands were vascularly perfused and secretion induced by 10M ACh. Secretion was inhibited by 343% following perfusion with the general K+ channel inhibitor Ba2+ (5mM), whereas organic inhibitors of BK (200nM paxilline) or intermediate-conductance (IK) K+ channels (5M clotrimazole) had no effect. Secretion was strongly influenced by Cl channel inhibitors, as 100M 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) completely abolished, while 10M NPPB, 20M NS1652 and 20M NS3623 reduced secretion by 343%, 233% and 594%, respectively. In conclusion, although high expression levels of BK channels were demonstrated, pharmacological tools failed to demonstrate any role for BK, IK or SK channels in salivary secretion in the rabbit submandibular gland. Other types of K+ channel, however, and particularly Cl channels, are essential for ACh-induced salivary secretion.