The isolated urinary bladder of the toad responds to neurohypophyseal hormone with a net increase of water transport from the mucosal to the serosal solution in the presence of an osmotic gradient. This response is mediated intracellularly by cyclic 3',5'-adenosine monophosphate (AMP). The present study demonstrates that hydroosmotically active substances such as oxytocin, dibutyryl cyclic 3',5'-AMP, and theophylline, but not hydroosmotically inactive substances, induce the uptake of horseradish peroxidase from the mucosal solution. Peroxidase taken up by the mucosal cells is demonstrable in small tubules and vesicles, and eventually accumulates in lysosomes. The uptake of peroxidase from the serosal solution into similar bodies in the mucosal cells is not hormone-dependent. It is also shown that peroxidase does not penetrate the tight junction from either the mucosal or serosal solution. These results extend previous findings which implicated the apical membrane of the mucosal epithelium as the site affected by neurohypophyseal hormones. A mechanism based on secretory phenomena is proposed as a framework for future investigations of apical membrane permeability changes and pinocytosis.