The glycoprotein secretion from the mouse gallbladder epithelium induced by vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) was investigated by electron microscopic morphometry. Both VIP and CCK caused a decrease in the volume density of the glycoprotein-containing granules of the principal cells. The effect on the gallbladder epithelium of a left-sided vagotomy was examined. Three and six weeks postvagotomy, slight decreases in cell and nuclear profile area and secretory granule volume density were noted. CCK induced a secretion of glycoprotein granules, whereas no such secretory effect due to VIP could be detected in animals 3 and 6 weeks after vagotomy. The results demonstrate that VIP, like CCK, is involved in glycoprotein secretion from the mouse gallbladder epithelium, but the secretory effect of VIP would appear to be dependent on an intact vagal innervation. The results are of interest in relation to the hypothesis that glycoprotein release may be a precipitating factor in the production of gallstones.