Electrophysiological properties of mouse bone marrow-derived mast cells (BMMC) were studied under the whole-cell clamp configuration. About one third of the cells were quiescent, but others expressed either inward or outward currents. Inwardly rectifying (IR) currents were predominant in 14% of the cells, and outwardly rectifying (OR) currents in 24%. The rest (22%) of the cells exhibited both inward and outward currents. The LR currents were eliminated by 1 mM Ba2+, and were partially inhibited by 100 mu M quinidine. The reversal potential was dependent on extracellular K+, thereby indicating that K+ mediated the IR currents. The negative conductance region was seen at potentials positive to E(K). The OR currents did not apparently depend on the extracellular K+ concentration, but were reduced by lowering the extracellular Cl- concentration. The OR currents were partially blocked by 1 mM Ba2+, and were further blocked by a Cl- channel blocker, 4,4-'diisothiocyano-2,2'-stilbenedisulfonate (DIDS). In addition, the reversal potential of the OR currents was positively shifted by decreasing the ratio of external and internal Cl- concentrations, suggesting that Cl- was a major ion carrier. In cells exhibiting IR currents, the membrane potential varied among cells and tended to depolarize by elevating the-external Kf concentration. In cells with OR currents, the resting potential was hyperpolarized in association with an increase in conductance. These results suggest that:BMMC have a heterogeneous electrophysiological profile that may underlie a variety of ion channels expressed in different phenotypes of mast cells. Activities of both the inwardly rectifying K+ channel and the outwardly rectifying Cl- channel seem to contribute to the regulation of the membrane potential.