A number of invertebrate venoms have been tested for effects on M-type K + currents ( I K( M) ) in differentiated mouse neuroblastoma X rat glioma NG108-15 cells. Among the venoms tested, Buthus eupeus scorpion venom reversibly inhibited I K( M) by ∼ 44% at 50 μg/ml. Inhibition was not due to activation of bradykinin or nucleotide (pyrymidine) receptors. On venom fractionation, a polypeptide of 4 kDa was purified that inhibited I K( M) by ∼45% with an IC 50 of ∼;33 nM. Neither the crude venom nor the purified polypeptide affected the Ca 2+ current or the delayed rectifier K + current. While the crude venom prolonged the Na + current, the polypeptide did not. Thus, the 4 kDa Buthus eupeus polypeptide appears to be a selective inhibitor of I K( M) in NG108-15 cells.