The ionic mechanism of the effect of intracellularly injected adenosine 3',5'-cyclic monophosphate (CAMP) on the membrane of identified neuron L5 of Apl ysia kurodai was investigated with conventional voltage-clamp and ion-substitution techniques. The intracellular elevation of CAMP caused an inward current ('CAMP), which was not accompanied by a significant change in membrane conductance at potentials more hyperpolarized than -60 mV. The current increased over the voltage range (-50 to -30 mV) associated with a conductance decrease and decreased at potentials more hyperpolarized than -60 mV. Elevated intracellular CAMP was found to enhance a region of negative slope resistance in steady-state I -V relations. Duration of the 'CAMP was greatly prolonged by bath-applied isobutylmethylxanthine (50 ,uM), but imidazole (10 mM) had an opposite effect on the 'CAMP. Tolbutamide (5 mM), a protein kinase inhibitor, reduced the DAMP. The current was not affected by the presence of bath-applied TTX (50 µM), ouabain (50 /LM), or triaminopyrimidine (5 mM). Reduction of [Na+]o reversibly decreased the DAMP. Li+ could largely substitute for Nat Alterations of [K+]o, and bath application of 4-AP (5 mM) and TEA (30 mM) did not affect the DAMP, In the presence of Nat, Cl-, and divalent cations such as Ca2+ and Ba2+ inhibited the DAMP. These results suggest that fast elevation of intracellular cAMP induces a TTX-resistant slow Na+ inward current, and the current might be due to activation of CAMP-dependent protein kinase.