Ion secretion in guinea pig gall-bladder epithelium can be electrogenic. Therefore ion channels were studied utilizing the patch-clamp technique. Using the cell-attached configuration on dissociated cells, K+ channels with a single-channel conductance of about 160 pS, for negative voltage values, were identified. An inward rectification was usually observed. The channel open probabilities at physiological voltage values were low (less than 0.1) and increased 3- to 4-fold with depolarization of 20-30 mV. Using inside-out configuration and symmetrical 145 mM KCl, the I/V curve was linear and was not modified by the presence of Mg2+ and ATP on the cytoplasmic side. The channels were selective for K+ over Na+ (P-Na+/(PK+)=0.05). They were activated by increased levels of [Ca2+] or pH on the cytoplasmic side. Data suggest that the activity of these channels is not only influenced by voltage, [Ca2+], pH but also by unidentified cytoplasmic factors responsible for the inward rectification.