1. To explore the role of atrial natriuretic factor (ANF) in the response to an acute saline load, we compared plasma hormone and urinary electrolyte interrelationships during administration of ANF and saline. Plasma concentrations of ANF, renin, angiotensin II and aldosterone, together with urine volume and electrolytes, were measured during infusions of placebo, ANF [alpha-human ANF (99-126)] and 0.9% (w/v) NaCl solution in normal subjects under standardized conditions of diet and posture. 2. Saline loading and ANF infusions initially induced similar natriuresis and suppression of renin-angiotensin-aldosterone system activity in association with markedly disparate values of plasma ANF. Plasma ANF levels rose to two- and eight-fold placebo values with saline and ANF, respectively (P less than 0.001). Conversely, in the period after infusion plasma ANF values were similar while natriuresis differed significantly. Peak natriuresis lagged behind peak plasma ANF values with both stimuli. 3. ANF, but not saline, enhanced urinary excretion of calcium and magnesium. Saline, but not ANF, caused increased kaliuresis. 4. The data suggest that ANF makes only a minor contribution to natriuresis induced by saline challenge, although full confirmation of this point requires quantification of end-organ responses to endogenous ANF in the face of changing arterial pressure and circulating volume.