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The perforated-patch whole-cell technique was used to record membrane currents in epithelial cells (9HTEo−) obtained from the human tracheal epithelium. Extracellular application of 2-chloroadenosine and ATP (0.01–100 μM) caused activation of Cl −currents similar to those regulated by cell volume in airway and intestinal cells. This response was inhibited by increasing extracellular osmolality, by omission of extracellular Ca 2+or by the addition of the A 2adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Fluorimetric measurements with fura-2 reveal that 2-chloroadenosine and ATP elicited both a Ca 2+influx through the plasma membrane and a release from intracellular stores.