Patch clamp methods and reverse transcription-polymerase chain reaction (RT-PCR) were used to characterize an apical K ؉ channel in Calu-3 cells, a widely used model of human airway gland serous cells. In cell-attached and excised apical membrane patches, we found an inwardly rectifying K ؉ channel (Kir). The permeability ratio was P Na /P K ؍ 0.058. In 30 patches with both cystic fibrosis transmembrane conductance regulator and Kir present, we observed 79 cystic fibrosis transmembrane conductance regulator and 58 Kir channels. The average chord conductance was 24.4 ؎ 0.5 pS (n ؍ 11), between 0 and ؊200 mV, and was 9.6 ؎ 0.7 pS (n ؍ 8), between 0 and 50 mV; these magnitudes and their ratio of ϳ2.5 are most similar to values for rectifying K ؉ channels of the Kir4.x subfamilies. We attempted to amplify transcripts for Kir4.1, Kir4.2, and Kir5.1; of these only Kir4.2 was present in Calu-3 lysates. The channel was only weakly activated by ATP and was relatively insensitive to internal pH. External Cs ؉ and Ba 2؉ blocked the channel with K d values in the millimolar range. Quantitative modeling of Cl ؊ secreting epithelia suggests that secretion rates will be highest and luminal K ؉ will rise to 16 -28 mM if 11-25% of the total cellular K ؉ conductance is placed in the apical membrane (Cook, D. I., and Young, J. A. (1989) J. Membr. Biol. 110, 139 -146). Thus, we hypothesize that the K ؉ channel described here optimizes the rate of secretion and is involved in K ؉ recycling for the recently proposed apical H ؉ -K ؉ -ATPase in Calu-3 cells.