Vasoactive intestinal polypeptide is known to have powerful effect on the secretions from endocrine and exocrine glands. By immunohistochemical studies on the rat, both a dense network of vasoactive intestinal polypeptide-immunoreactive nerve fibers around the acini of Brunner's glands, and small ganglia with vasoactive intestinal polypeptide-immunoreactive nerve-cell bodies close to the glands were demonstrated. Intravenous infusions of vasoactive intestinal polypeptide in doses of 10, 100, and 1000 ng/kg.h significantly increased flow rate, as well as bicarbonate and protein output from Brunner's glands in the rat. After infusion of vasoactive intestinal polypeptide the secretory cells, which in the control group were rich in PAS-positive mucin, became almost completely PAS-negative. It is suggested that physiologic secretion from Brunner's glands may be stimulated by the vasoactive intestinal polypeptidergic nerves.