In this study we examined by impalement techniques properties of the macroscopic K+ conductances in the luminal and basolateral membrane of principal cells from isolated perfused cortical collecting ducts (CCD) of the rat. Both membranes possess a dominating K+ conductance. Compared to their behaviour with K+, both membranes appear much less permeable to NH+4 and Rb+, and the K+ conductances of both membranes are inhibited by these cations. In light of these findings, it is very unlikely that significant amounts of NH+4, which is secreted in the CCD, cross the principal cells as NH+4. Several inhibitors with known effects on K+ channels in patch-clamp studies have been examined. Tetraethylammonium, which inhibits the excised K+ channels of these cells, has no effect on the macroscopic K+ conductances of either membrane. Verapamil, which inhibits the K+ channels in the luminal membrane, acts predominantly on the basolateral membrane K+ conductance in the intact tubule. Therefore, some of the macroscopic properties of the K+ conductances are distinct from those of single channels thus far observed in patch-clamp studies.