The whole cell perforated patch clamp technique was used to study membrane currents in isolated rabbit corpus cavernosum smooth muscle cells. Depolarization from -80 mV to the range -40 to -10 mV evoked a nifedipine- sensitive Ca2+ current that was followed by a slower inward current that activated over several hundred ms. The slow current reversed near the Cl- equilibrium potential (ECl) and was reduced by anthracene-9- carboxylic acid (A9C; 1 mM) and niflumic acid (100 µM), suggesting that it was a Ca2+-activated Cl- current. When held constantly at -60 mV, over 70% of cells fired spontaneous transient inward currents (STICs), the amplitudes of which were reduced by A9C and niflumic acid. STICs reversed near ECl in a symmetrical Cl- gradient and when [Cl-]o was substituted with glutamate or I-, the reversal potential shifted to more positive or more negative values, respectively, confirming that STICs were mediated by Cl- channels. STICS were also blocked by cyclopiazonic acid, 2-aminoethoxydiphenyl borate (2-APB) and 2-nitro-4-carboxyl-N,N- diphenylcarbamate (NCDC), suggesting that they depended on IP3-mediated Ca2+-release from the sarcoplasmic reticulum. Modulation by the NO/cGMP pathway was investiated by applying L-nitrosocysteine, (3-(5- hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1), and 8- bromo cGMP, all three of which abolished STIC activity. YC-1 also reduced noradrenaline-evoked inward currents, but had no effect on similar currents evoked by caffeine, suggesting that cGMP selectively inhibited IP3- mediated Ca2+ release. We propose that Ca2+-activated Cl- currents underlie detumescent tone in the corpus cavernosum, and that modulation of this mechanism by the NO/cGMP pathway is important during penile erection.