Characteristics of sodium transport in the inner medullary collecting duct were determined in anesthetized rats before and during intravenous infusion of synthetic atrial natriuretic factor (atriopeptin II). Infusion of the factor was associated with increased sodium delivery and reduced fractional reabsorption in the duct. Increasing delivery to the same extent by KCl infusion had no effect on fractional reabsorption. The results demonstrate that atrial natriuretic factor has a specific inhibitory effect on net sodium transport in this part of the nephron. The mechanism of this inhibition may involve induction of sodium permeability and consequent backflux into the tubular lumen.