In vivo microperfusion techniques were employed in anesthetized rats to determine whether K secretion by renal distal tubules requires the presence of Na in luminal fluid, and, if it does, in what concentration range do changes in Na concentration have the most effect. In a first series of experiments Na in perfusion fluid was replaced at constant Cl with tetramethylammonium (TMA). When the perfusion fluid Na concentration was reduced from 96 or 34 mM to 10 or 3 mM, K secretion was reduced by 50-60% and transepithelial voltage ( VTE ) was reduced by 40-60%. In a second series of experiments, in which NaCl was replaced with urea, perfusion fluid Na concentration again was reduced to 3 mM, and K secretion and VTE were reduced. In a third series of experiments, Na was replaced with rubidium. The reduced K secretion could not be explained solely by changes in electrical driving forces. The results indicate that some luminal Na (half-maximal concentration approx 10 mM) is necessary to permit K secretion to proceed at a normal rate. Considering prior measurements of luminal Na concentration in rat distal tubules, it is unlikely that changes in luminal Na concentration play an important role in regulating the rate of distal K secretion.