The effect of hydrostatic pressure on ion transport in the bladder uroepithelium was investigated. Isolated rabbit uroepithelium was mounted in modified Ussing chambers and mechanically stimulated by applying hydrostatic pressure across the mucosa. Increased hydrostatic pressure led to increased mucosal-to-serosal Na+ absorption across the uroepithelium via the amiloride-sensitive epithelial Na+ channel. In addition to this previously characterized pathway for Na+ absorption, hydrostatic pressure also induced the secretion of Cl- and K+ into the mucosal bathing solution under short-circuit conditions, which was confirmed by a net serosal-to-mucosal flux of 36Cl- and 86Rb+. K+ secretion was likely via a stretch-activated nonselective cation channel sensitive to 100 microM amiloride, 10 mM tetraethylammonium, 3 mM Ba2+, and 1 mM Gd3+. Hydrostatic pressure-induced ion transport in the uroepithelium may play important roles in electrolyte homeostasis, volume regulation, and mechanosensory transduction.