A single BPSP (excitatory-inhibitory postsynaptic potential) was monosynaptically produced in an identified Onchidium neuron, Be-1, with a beating rhythm upon stimulation of the cardiac nerve. The BPSPs summated to produce an inhibition of long duration (ILD) upon blockage of the beating rhythm after repeated stimulation, so that the BPSPs seemed to be functionally inhibitory. Ten stimuli (1-2 Hz) applied to the cardiac nerve usually evoked an ILD (0.5-1 min) of about 10 mV. The early and middle phases of this ILD reversed near -80 to -85 mV, but the late phase did not reverse at more negative potentials. None of the phases was significantly affected by low Cl or Na solutions or by high Ca solutions. However, by changing the external K, the shift of the reversal potentials for the early and middle phases reached about 65% of that predicted for the K electrode, although the late phase was insensitive to the external K. Intracellular tetraethylammonium (TEA) attenuated the amplitude of the ILD but did not shorten the duration. These suggest that the ILD has another conductance-independent mechanism simultaneously with the increase in K conductance. Several lines of evidence suggested that a ouabain-sensitive Na pump does not contribute to the ILD. Inhibitors of energy supply, 2,4-dinitrophenol sodium salt (DNP) and cyanide, selectively and reversibly reduced the ILD. Simultaneous applications of intracellular TEA and DNP completely abolished the ILD. As for the ionic basis, the histamine-induced inhibitory response in Be-1 was closely related to the ILD. Cimetidine specifically blocked the ILD and histamine-induced inhibitory response, which were mimicked by 2-methylhistamine, but not by dimaprit. It is concluded that the ILD, mediated by some histamine receptor other than the H1 or H2 type, results from an increase in K conductance and a hyperpolarizing ion pump insensitive to ouabain.