Inbred Dahl salt-sensitive rats had a higher content of atrial natriuretic factor by bioassay in their atria than did inbred Dahl salt-resistant rats. This finding was true both in young 1- to 2-month-old rats, when blood pressure differences between strains were small, and in 7-month-old rats, when blood pressure differences were marked. Atria from salt-sensitive rats had more atrial natriuretic factor than did atria from salt-resistant rats when the rats were fed either low (0.3% NaCl) or high (8% NaCl) salt diet, but a high salt diet suppressed the atrial content of atrial natriuretic factor equally in both strains. In young, prehypertensive salt-sensitive rats, intravenous injections of atrial natriuretic factor caused significantly less natriuresis and diuresis than in salt-resistant rats (p less than 0.05). As the rats aged and salt-sensitive rats became markedly hypertensive, the strain responses to atrial natriuretic factor were reversed, that is, the salt-sensitive rats became more sensitive to atrial natriuretic factor than did the salt-resistant rats. Aortic vascular smooth muscle response to contraction with KCl was equally inhibited in both strains by atrial extracts or atriopeptin II. Thus, the salt-sensitive rat renal hyporesponsiveness to atrial natriuretic factor was not associated with a generalized hyporesponsiveness of vascular tissue to atrial natriuretic factor. It is argued that salt-sensitive rats could have two defects relating to atrial natriuretic factor, one involving hyporesponsive kidneys and another involving decreased release of atrial natriuretic factor from the atria.