We have cloned a novel inward rectifier K+ channel (hIRK2) from a human frontal cortex cDNA library. The amino acid sequence of hIRK2 shares 60% and 40% identity with the mouse IRK1 and the rat ROMK1 channels, respectively. Xenopus oocytes injected with hIRK2 cRNA showed an inwardly rectifying K+ current that had a prominent 'N-shape' I-V curve and was blocked by extracellular Ba2+. The hIRK2 channel has two unique features: (a) an 18 amino acid insertion between the first transmembrane region and the pore, and (b) restricted mRNA distribution found only in human brain and heart.