Low rates of unilateral renal arterial infusion with isotonic saline (154 mM NaCl) produce a natriuresis in both kidneys in anesthetized rats, with the involvement of a blood-borne factor. We investigated whether this response was modulated by known renal or adrenal hormones. The response to saline infusion at 0.05 ml/min was tested after acute adrenalectomy (n = 7), in the presence of various blocking agents [captopril (3 mg.kg-1.h-1, n = 7), indomethacin (5 mg/kg, n = 8), aprotinin (25 KIU/min, n = 8), propranolol (1 micrograms/min, n = 6), or benserazide (15 micrograms/min, n = 6)], and after lignocaine infusion around the renal artery (12.5 micrograms/min, n = 5). In all cases, the overall increase in sodium excretion by both kidneys was not significantly less (alpha < or = 0.01) than that in untreated rats; it was increased by aprotinin, renal nerve blockade, and propranolol. Plasma levels of angiotensin II, aldosterone, and atrial natriuretic peptide were unchanged by renal arterial saline infusion. We conclude that the saline-induced natriuresis is not reduced by inhibition of the production of angiotensin II, prostaglandins, kinins, dopamine, or adrenal hormones, or by factors released by the renal nerves, indicating that none of these is directly responsible for the saline-induced natriuresis.