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 A 2 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 retool/1 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 (Ro). Removal of phenylalanine leads to rapid hyperpolarization, increase of Ra and decline Re. Mepacrine (100 ~tmol/1) depolarizes the cell membrane and increases the peritubular cell membrane resistance (Rb) , R c and the intracellular pH. In the presence of mepacrine, phenylalanine leads to a sustained depolarization and a transient decrease of R,. Indomethacin (10 gmol/1) 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 lamol/1) does not alter significantly PDv, Ra, Rb or Ro prior to phenylalanine. However, in the presence of nordihydroguaiaretic acid, the repolarization upon phenylalanine is significantly more rapid, and the removal of phenylalanine in the presence of nordihydroguaiaretic acid is followed by a significant decrease of both, Ra and R b. The observations point to an involvement of eicosanoids in the regulation of ion conductances during stimulation of sodium-coupled transport.