Methylmercury (MeHg) is generally known as a neurotoxic heavy metal while its effect on alveolar macrophages is still rarely studied. In this paper, we attempted to use whole cell and cell-attached patch-clamp recording technique and fura-2 fluorescence measurement to elucidate the effects of MeHg on rat alveolar macrophages. The results showed that extracellular application of MeHg induced a transient outward current I O (MeHg), 10-20 s in duration, 100-1000 pA in amplitude at -40 mV associated with a marked increase in conductance. The reversal potential depended distinctly on the external K + concentration. Removal of external Ca 2 + as well as applied verapamil caused a depression of I O (MeHg), and intracellular dialysis with 5 mM EGTA completely abolishedI O (MeHg). Heparin (5 mg/ml) applied by intracellular dialysis greatly accelerated a run-down of I O (MeHg) induced by pressure ejection of MeHg. K + channel blockers such as quinine, and 4-aminopyridine especially low concentrations of dequalinium and apamin, but not tetraethylammonium inhibited I O (MeHg). Cell-attached single-channel recordings with the pipette solution containing 145 mM KCl revealed that the activation of single-channel currents with a conductance of 12 pS could be induced by application of MeHg outside the patch. Since MeHg increased [Ca 2 + ] i , in a concentration-dependent manner which was partially blocked by either verapamil or Ca 2 + -free medium containing 1 mM EGTA, it is concluded that MeHg activates a Ca 2 + -dependent K + conductance by an increase of [Ca 2 + ] i through an influx from outside the cells as well as mobilization from intracellular store. A possibility that this membrane hyperpolarizing K + current may exhibit a functioning modulator in response to the harmful cytotoxic increase in [Ca 2 + ] i caused by MeHg was tested. Accordingly, this working hypothesis is verified by an increase of MeHg-induced cytotoxicity of cultured rat alveolar macrophages through a blockade of this Ca 2 + -activated K + channel by dequalinium.