Whole-cell voltage and current clamp recordings were obtained from cortical neurons of the pond turtle, Pseudemys scripta elegans. Norepinephrine (NE) induced an outward current in 50% of pyramidal neurons. This current had a reversal potential of -88.3 +/- 3.2 mV, consistent with a K+ conductance increase, and had a mean amplitude of 18.3 +/- 7.2 pA at -40 mV. The ionic dependence and pharmacological analyses are both consistent with alpha 2 adrenergic receptor stimulation. Inhibition of Na(+)-dependent action potentials with TTX did not diminish the NE-induced K+ conductance, indicating that NE acts directly on the postsynaptic neuron. In addition to effects on postsynaptic conductance, NE dramatically decreased the amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in 55% of pyramidal neurons. The decrease in spontaneous IPSCs was observed both in those neurons which exhibited an increase in K+ conductance in response to NE administration (81%) and in those which did not (33%). Thus, NE modulates neuronal excitability both directly by activating a postsynaptic K+ conductance and indirectly by decreasing spontaneous IPSCs.