Hydrochloric acid (HC1) secretion by gastric parietal cells involves an apical CI-conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cellattached membrane patches on cultured huma n gastric cells (HGT-1). In the cell-attached configuration (CI-149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (-0,7 pA) at zero holding potential and a reversal potential of + 24 mV, consistent with the presence of a CI-conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a -21 mV shift of their reversal potential when bath CI-was decreased from 149 mmol/1 to 53 mmol/1 (calculated Cl-:cation permeability ratio 17:1), and (iii) were highly sensitive to the CI-channel blocker diphenylamine-2-carboxylic acid (DPC, 10 -3 mol/1). This cAMP-activated CI-channel bears many similarities to other C1-channels within intestinal epithalia, and may ~epresent the apical C1channel operating in HCl-secreting gastric parietal cells.