The present study was performed to test the influence of sodium coupled transport of neutral substrates on intracellular pH and sodium activity in proximal tubules of the amphibian kidney. To this end, kidneys of rana esculenta have been isolated and perfused both through the portal vein (peritubular capillaries) and the aorta (luminal perfusate). The potential difference across the peritubular membrane of proximal tubule cells has been reduced with conventional (PDpt) as well as with sodium (PDna) and hydrogen ion (PDh) selective microelectrodes continuously before, during, and after the luminal application of 10 mmol/l phenylalanine, replacing 10 mmol/l raffinose. PDh and PDna allowed the calculation of intracellular pH (pHi) and sodium activity (Nai), respectively. In the absence of phenylalanine in the tubule lumen, PDpt approximates -57.5 +/- 2.3 mV (n = 27), pHi 7.73 +/- 0.04 (n = 14, extracellular pH 7.77), and Nai 13.3 +/- 0.9 mmol/l (n = 13, extracellular sodium activity 74 mmol/l). Within 1 min the luminal application of phenylalanine leads to a depolarisation of PDpt by +32 +/- 2 mV, as well as an increase of pHi by 0.24 +/- 0.04 and of Nai by 5.2 +/- 1.0 mmol/l. At 8 min from luminal application of phenylalanine, Nai plateaus 5 +/- 1 mmol/l above control value, PDpt increases again to a value of +12 +/- 2 mV below and pHi decreases to a value 0.04 +/- 0.07 above their respective control values. All changes are fully reversed after removal of phenylalanine from the tubule lumen.(ABSTRACT TRUNCATED AT 250 WORDS)