Using the patch-clamp technique, we have identified two types of chloride channel on duct cells cultured from human fetal pancreas. The channel we observed most frequently exhibited slight outward rectification, had a conductance of 4-7 pS in cell-attached patches, and was present on the apical plasma membrane where it usually occurred in clusters. Its open-state probability was not markedly voltage dependent but was increased up to threefold by exposing duct cells to secretin (10 nM), dibutyryl cyclic AMP (1 mM), or forskolin (1 microM). The other type of chloride channel was only rarely observed. Its current-voltage relationship exhibited marked outward rectification, giving chord conductances of 19 pS for inward currents and 53 pS for outward currents. Although this channel could be activated by sustained depolarization of excised patches, once activated the open state probability was not voltage dependent. While the physiological role of these channels is not firmly established, the small-conductance channel might function in parallel with a Cl- -HCO-3 exchanger to provide a mechanism for electrogenic bicarbonate secretion from the duct cell.