Microelectrode methods were used to assess the Na-dependent effects of mineralocorticoids on the conductive transport properties of cortical collecting ducts (CCD) from adrenalectomized (ADX) rabbits. Rabbits were divided into four groups: control, 3 h treatment with deoxycorticosterone (DOCA), 18 h DOCA treatment, and 18 h DOCA plus amiloride treatment. After only 3 h of DOCA treatment the transepithelial potential (VT) increased significantly from -1.4 to -8.7 mV, and after 18 h VT increased further to -19.3 mV. The basolateral membrane potential (Vb) significantly increased after 18 h (from -61.6 to -87.6 mV). However, compared with treatment with DOCA alone for 18 h, both -VT and -Vb were significantly attenuated with DOCA plus amiloride treatment to -8.3 and -72.9 mV, respectively. The apical membrane Na and K currents (INaa and IKa) and conductances (GNaa and GKa) were all increased after 3 h DOCA treatment. After 18 h of DOCA treatment, IKa, INaa, and GKa increased further, but GNaa remained unchanged. On simultaneous treatment with DOCA and amiloride, the maximum pump current (Ipmax), IKa, INaa, and GKa but not GNaa were all reduced significantly. These results support a mechanism whereby mineralocorticoids first increase GNaa. A rise in cell Na results then in the simultaneous increase in GKa and sodium transport, probably by insertion of new Na pumps. An additional direct effect of DOCA on GKa and Ipmax is not excluded.