The effects of cocaine on electrophysiological activity were examined in the CA1 region of the in vitro hippocampal slice. Low concentrations of cocaine (0.25-2.5 microM) had no direct effect on evoked potentials, but potentiated responses to threshold concentrations of norepinephrine (NE; 0.5 microM); this effect was also seen with other inhibitors of catecholamine uptake such as desipramine. The ability of low doses of cocaine to augment the changes in population spike amplitude elicited by NE appeared to be related to the ability of cocaine to block the uptake of NE into the noradrenergic nerve terminals in the rat hippocampus. Higher concentrations of cocaine (5-200 microM) elicited responses consistent with local anesthetic actions on neuronal membranes.