In excised inside-out membrane patches of the human colon carcinoma HT-29cl.19A cells a large conductance (373 +/- 10 pS) chloride channel was found. Channel activity could only be observed after excision of patches from cells incubated with calcium ionophore. The channel was never observed in cell-attached patches. The channel was strongly voltage dependent, being open only between +30 and -30 mV clamp potentials. The selectivity sequence among anions, deduced from reversal potentials, was I > Br > Cl > F > gluconate. The PNa/PCl was 0.09. Although a similar type of channel has been described earlier, this is the first report stating its appearance in patches of intestinal epithelial cells requiring the combined action of Ca2+ ionophore and excision, suggesting its control by an intracellular compound.