Angiotensin II (ANG II) is a powerful effector agent in the regulation of extracellular volume and exerts an important influence on renal sodium excretion. In addition to its effects on aldosterone secretion, ANG II acts directly on the kidney causing retention of sodium at low (physiological) doses and enhanced sodium excretion at high doses. The mechanism for these responses involves vasoconstrictor actions of ANG II on the renal vasculature and a direct action of the peptide on tubular reabsorption. Micropuncture and microperfusion studies have demonstrated that proximal tubular sodium and water transport are stimulated by physiological concentrations (10(-12) to 10(-10) M) of ANG II on the peritubular side, whereas higher doses (10(-7) M) cause inhibition. A luminal site of action in the proximal tubule has also been reported and additional more distal sites are indicated. [125I]ANG II binding sites on the brush border and basolateral membranes of proximal tubule cells have high affinity (Kd in the nanomolar range) for ANG II and lower affinity for ANG III. The biphasic action of ANG II is exerted directly on the epithelial cells and appears to be electroneutral. The data indicate that ANG II binds to receptors on the basolateral cell membrane and alters the rate of entry of sodium through the luminal membrane to increase or decrease, depending on the concentration of peptide. Several possible cellular mechanisms that could mediate these responses are discussed.