The effects of 20 mumol/l amiloride, 10 mumol/l furosemide and 1 mmol/l ouabain on cell Na and K concentrations were investigated by flame microphotometry in isolated rat medullary collecting tubules and medullary thick ascending limbs (MCT and MAL) as a function of the external potassium concentration [Ke]. The results are expressed as Na and K concentrations per liter cell volume ([Nac] and [Kc], mmol/l) and relative sodium content, [Nac]/([Nac] + [Kc]). From the experimental curves, [Ke]1/2 is defined as the [Ke] value corresponding to half maximal exchange of K against Na in cells. When [Ke] was 5 mmol/l, the relative Na content was less than 15% in control and amiloride-treated MCT as well as in control and furosemide-treated MAL, and about 24% in ouabain-treated MCT and MAL. In MCT, relative cell Na content increased up to 90% or more when [Ke] was reduced from 2.5 to 0.25 mmol/l. [Ke]1/2 was 0.55, 0.45 and 1.25 mmol/l for control, amiloride-treated and ouabain-treated MCT respectively. In MAL, similar increases in relative Na content were observed when [Ke] was reduced from 0.5 to 0.05 mmol/l. [Ke]1/2 was 0.25, 0.10 and 1.75 mmol/l for control, furosemide-treated and ouabain-treated MAL respectively. When [Ke] was reduced from 5 to 1 mmol/l, [Nac] dropped from 16.4 to 8.4 mmol/l (P less than 0.01) in control MAL. When [Ke] was 5 mmol/l, [Nac] was lower in furosemide-treated MAL (7.8 mmol/l) than control MAL (P less than 0.01). At 1 mmol/l [Ke], [Nac] was similar in both groups. These results are discussed in terms of the balance between the active and passive components of Na and K fluxes across apical and basolateral cell membranes. They indicate that a K-dependent passive Na entry process exists in the membranes of MAL cells but not of MCT cells. This process was proportionally more inhibited than the active Na pump when [Ke] was reduced from 5 to 1 mmol/l. In addition, it was found sensitive to furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)