3,3′‐diallyldiethylstilbestrol (DADES), a blocker of the facilitated diffusion of glucose, was found to interfere markedly with the hydrosmotic response to antidiuretic hormone and its related agonists. Frog urinary bladders were isolated and monitored for transmural net water flow. DADES was added either to the serosal or to the apical medium at concentrations ranging from 10−4M to 10−6M. Pretreatment for 30 min with apical 10−4M DADES drastically reduced the subsequent hydrosmotic response:(a)to oxytocin (4.4×10−8M) by 91.7±17.6% versus 6.2±7.8 in control;(b)to 8‐bromo 3′,5′‐cyclic AMP by 93.5±19.4% versus 19.4±11.4%;(c)to serosal hyperosmolarity (mannitol 220 mOsm) by 99.3±0.5% versus 12.3±18.2%.This effect was dose‐dependent. Inhibitory action of DADES was more effective on the apical side than on the serosal side (97.0±1.5 versus 45.8±10.8). Freeze‐fracture studies revealed a modified distribution of the particles and unusual endocytotic pits and vesicles in the apical membrane of both granular and mitochondria‐rich epithelial cells. These observations point to multiple and complex effects of the drug. Thus, it seems that DADES has numerous effects on urinary epithelium, which makes it a nonspecific inhibitor of water permeation. Conclusions on its use should theref