In the rat parotid gland, an atropine-resistant parasympathetic-nerve-evoked secretion was demonstrated in vivo. In the absence of atropine, the non-adrenergic, non-cholinergic transmitter release seemed to contribute to the fluid secretion and to be largely responsible for the secretion of amylase and acinar secretory granules. The gland was reached by nerve fibers containing substance P (SP), vasoactive intestinal peptide (VIP), and, to some extent, calcitonin-gene-related peptide (CGRP) via the parasympathetic auriculo-temporal nerve. Upon electrical stimulation of the nerve, these peptides were released. SP and substance K (SK), a novel tachykinin, induced a profuse watery secretion when injected i.v., while VIP caused a sparse but amylase-rich secretion. CGRP caused no secretion on its own. The tachykinin-evoked secretory response was enhanced by VIP and CGRP. A SPanalogue almost abolished the SP-evoked response, while the atropine-resistant parasympathetic response was only halved. None of the peptides under study can on its own account for the atropine-resistant parasympathetic secretion. The neuropeptides may play complementary roles in the regulation of the exocrine functions of the gland.