In whole-cell recordings from CA1 neurons, net outward currents (at ca. -20 mV, from VH ca. -50 mV) were 40-50% depressed by sodium nitroprusside (100-500 microM) or L-arginine (L-ARG; 50-200 microM), but not by D-arginine (100 microM). The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM) restored the L-ARG-depressed current to ca. 80% of control. In naive cells, L-NAME increased outward currents by 45 +/- 12.6%; the enhanced currents were then reduced by adding L-ARG (200-400 microM). The NO-sensitive current is Ca-dependent, because L-NAME and L-ARG were ineffective in Mn/low Ca medium or when electrodes contained 2.2 mM EGTA. Since high voltage-activated Ca-currents were unaltered by L-NAME, we conclude that NO tonically enhances excitability in slices by depressing a voltage- and calcium-dependent (IK(Ca)-type) outward current.