Effects of sodium nitroprusside in the rat cortical collecting duct are independent of the NO pathway. Recently we described K⁺ channels in the basolateral membrane of principal cells of rat cortical collecting duct (CCD) which are regulated by a cGMP-dependent protein kinase (Pflügers Arch 429:338–344, 1995). We examined the effects of the NO-liberator sodium nitroprusside (SNP) on single channel activity and membrane voltage (V_m) in principal cells of rat CCD, and on transepithehal voltage, lumen-to-bath Na⁺ fluxes, and osmotic water permeability in isolated perfused rat CCD tubules. While in patch clamp experiments SNP (10 µM) hyperpolarized principal cells from -54 ± 10 mV to -71 ± 5 mV (N = 5) and increased the activity of the described K⁺ channels from 0.05 ± 0.03 to 0.45 ± 0.14 (N = 5) in cell-attached and from 0.04 ± 0.02 to 0.25 ± 0.05 (N - 4) in excised patch clamp experiments, it had no effect on basal or AVP-dependent transepithehal voltage, Na⁺ fluxes, or the osmotic water permeability. In addition, neither 50 µM SIN-1, another liberator of NO, nor 1 mM L-NAME, an inhibitor of the NO-synthase, changed V_m significantly. Furthermore, in cGMP-assays SNP failed to increase intracellular cGMP in CCD segments. Thus, we conclude that in the rat CCD transport is not regulated via the NO-pathway and that SNP acts as an cGMP independent activator of K⁺ channels in the basolateral membrane of these cells.