Principal cells of mouse gallbladder epithelium were subjected to a quantitative electron microscope study after in vivo and in vitro exposure to pilocarpine, noradrenaline, atropine, and phenoxybenzamine. Stereologic measurements were performed on randomly selected principal cells, and special interest was paid to changes in the size of the secretory granule population of the cells. Thirty minutes after in vivo and in vitro stimulation with pilocarpine, there was a significant decrease of the volume density of the glycoprotein-containing granules in the principal cells. Thirty minutes after in vivo administration of the cholinergic antagonist atropine, a significant increase of this parameter was observed. In vitro incubation for 30 min with a combination of pilocarpine and atropine extinguished the pilocarpine-induced effect on the secretory granules. Noradrenaline and phenoxybenzamine (an alpha-adrenergic blocking agent) in vivo and in vitro (30 min) had no effect on the volume density of the secretory granules. The authors' findings suggest that principal cells of the mouse gallbladder epithelium exhibit an increased rate of secretion of glycoprotein granules after stimulation in vivo and in vitro with cholinergic agents, whereas adrenergic agents are without effect.