Rats with hypokalemia induced by eating a low-K diet have a diminished kaliuretic response to mineralocorticoids. The purpose of this study was to determine if this was the due to a lower rate of net secretion of K in the cortical collecting duct (CCD) and/or an enhanced rate of reabsorption of K in the medullary collecting duct (MCD). Secondary active secretion of K in the CCD raises the [K] in the lumen as compared to the plasma [TF/P)K). If the (TF/P)K is greater than 1, there was secondary active secretion of K in this nephron segment. The (TF/P)K in the CCD was measured by microcatheterization of the collecting duct. Three groups of rats were studied: rats on a low-K diet with and without the acute administration of DOCA, and rats on a normal-K diet treated with DOCA on a chronic basis. Rats on the low-K diet had a (TF/P)K of 0.8 +/- 0.11; this value did not rise to values significantly greater than 1 after the acute administration of DOCA (1.4 +/- 0.35). In contrast, chronic administration of DOCA to rats fed a normal-K diet did result in a (TF/P)K which was significantly greater than unity (3.1 +/- 0.39). The degree of hypokalemia was not significantly different in these rats. The absolute and fractional reabsorption of K in the MCD was not different in the rats on the low-K diet with or without DOCA. We conclude that the nephron segment which is responsible for the reduced kaliuretic response to mineralocorticoids is the CCD.