In proximal renal tubules of the frog kidney, stimulation of sodium-coupled transport leads to a depolarization of the peritubular cell membrane, followed by partial repolarization. These alterations of the potential difference across the peritubular cell membrane (PDpt) are in part the result of altered peritubular potassium conductance. The repolarization has been blunted by the phospholipase A2 inhibitor mepacrine, but not by the cyclooxygenase inhibitor indomethacin. In the present study the effect of mepacrine, indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid on the electrical properties of proximal renal tubules has been tested in the presence and absence of stimulated sodium-coupled transport. In the absence of inhibitors, addition of 10 mmol/l phenylalanine to the luminal perfusate leads to a rapid depolarization and partial repolarization of the peritubular cell membrane, a decrease of the luminal cell membrane resistance (Ra) and a small increase of the cellular core resistance (Rc). Removal of phenylalanine leads to rapid hyperpolarization, increase of Ra and decline Rc. Mepacrine (100 mumols/l) depolarizes the cell membrane and increases the peritubular cell membrane resistance (Rb), Rc and the intracellular pH. In the presence of mepacrine, phenylalanine leads to a sustained depolarization and a transient decrease of Ra. Indomethacin (10 mumol/l) does not significantly modify PDpt, the lumped resistance of both cell membranes (Rm) or Rc in the presence or absence of phenylalanine. Nordihydroguaiaretic acid (50 mumols/l) does not alter significantly PDpt, Ra, Rb or Rc prior to phenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)