Triamterene (2,4,7-triamino-6-phenylpteridine) is a potassium-sparing diuretic whose mechanism of action is not clear. Experiments were performed to study the effect of triamterene upon the activity of Na-K-ATP-ase in the kidney plasma membranes. This enzyme, dissolved within the membrane bilayer, has been considered to be a biochemical vehicle for the active transport of sodium across the cell membrane. Intact and adrenalectomized rats were subjected to a five-day treatment with triamterene in a daily dose of 1.5 mg/100 g body weight. Triamterene was also administered to a group of intact, salt-loaded, rats. The activity of Na-K-ATP-ase in the kidney plasma membranes of intact and adrenalectomized rats treated with triamterene was decreased by 22.4% (p less than 0.05) and 37.2% (p less than 0.05), respectively. The activity of Na-K-ATP-ase in the renal plasma membranes of intact, salt-loaded, rats underwent greater decrease--63% (p less than 0.05). If the decreased activity of Na-K-ATP-ase in the kidney plasma membranes of rats treated with triamterene manifested the diuretic action of triamterene, results obtained in adrenalectomized rats would suggest that triamterene acts directly on the kidney, not via the adrenal glands.