The effects of acetazolamide, amiloride, furosemide, ouabain and theophylline on nerve-induced prostatic secretion were determined in pentobarbital-anesthetized dogs. In one set of experiments the glands were exposed to normal saline or drug-containing saline between periods of nerve-induced secretion by connecting a urethral cannula for 30-min periods to a buret filled with normal saline or drug-containing saline at a height of 100 cm above the gland and by allowing retrograde penetration of these solutions into the gland. Secretion in response to stimulation of the hypogastric nerves at 20 Hz was markedly inhibited by intraurethral exposure to 0.1 and 1 mM ouabain but not to 10 mM furosemide, 3 mM amiloride or 30 mM theophylline; responses to stimulation at 2 Hz were potentiated by 30 mM theophylline. In other experiments, secretion in response to stimulation at 20 Hz was inhibited by i.v. administration of 10 to 30 mg/kg of furosemide but not 2 to 8 mg/kg of amiloride or 18.5 to 25 mg/kg of acetazolamide. Because active Cl- transport is a major process in canine prostatic fluid formation and because secretion of this fluid was selectively modified by these drugs in the same manner as is Na+,K+-coupled active Cl- transport by a variety of other epithelia, these epithelia appear to share a common Cl- transporting system.