We report the primary sequence of TASK-4, a novel member of the acid-sensitive subfamily of tandem pore K(+) channels. TASK-4 transcripts are widely expressed in humans, with highest levels in liver, lung, pancreas, placenta, aorta and heart. In Xenopus oocytes TASK-4 generated K(+) currents displaying a marked outward rectification which was lost by elevation of extracellular K(+). TASK-4 currents were efficiently blocked by barium (83% inhibition at 2 mM), only weakly inhibited by 1 mM concentrations of quinine, bupivacaine and lidocaine, but not blocked by tetraethylammonium, 4-aminopyridine and Cs(+). TASK-4 was sensitive to extracellular pH, but in contrast to other TASK channels, pH sensitivity was shifted to more alkaline pH. Thus, TASK-4 in concert with other TASK channels might regulate cellular membrane potential over a wide range of extracellular pH.