Conscious two-kidney, one clip rats with 150 mm Hg or higher systolic blood pressure were infused with saralasin for 60 minutes. Those with a blood pressure decline of 30 mm Hg or more were classified as saralasin-sensitive; those with a decrease of 10 mm Hg or less were considered saralasin-resistant. The animals were then housed in metabolic cages. Groups of sham-operated normotensive, saralasin-sensitive or saralasin-resistant two-kidney, one clip (2K1C) rats were infused with atrial natriuretic factor (Arg 101-Tyr 126), 100 ng/hr per rat, for 6 days. Corresponding control groups were sham-infused. Blood pressure was initially higher in the saralasin-sensitive groups (176 .+-. 6 and 181 .+-. 1 mm Hg, respectively) than in the saralasin-resistant groups (160 .+-. 4 and 169 .+-. 4 mm Hg, respectively). Atrial natriuretic factor infusion produced a gradual decline in blood pressure to 128 .+-. 5 mm Hg, but only in saralasin-sensitive 2K1C animals. Urinary volume, initially higher in saralasin-sensitive hypertensive than in normotensive rats, was depressed during atrial natriuretic factor infusion. Urinary sodium excretion and water intake showed the same tendency, but the changes were not significant. No such modifications were observed in saralasin-resistant or sham-operated rats infused with atrial natriuretic factor. Body weight, which was higher in normotensive activity 2K1C rats were the only group with higher plasma renin animals, was unchanged during atrial natriuretic factor infusion. Saralasin-sensitive, noninfused than sham-operated, normotensive controls. Plasma aldosterone was higher in the former than in the other five groups. Saralasin-resistant 2K1C rats, infused or not, or sham-operated rats infused with atrial natriuretic factor, had plasma aldosterone levels no different from those of normotensive controls. A positive correlation was noted between plasma renin activity and plasma aldosterone (r = 0.64, p < 0.001). The atrial content and conentration of immunoreactive atrial natriuretic factor were similar in all groups. These results suggest that the hypotensive response observed in saralasin-sensitive 2K1C rats during chronic atrial natriuretic factor infusion could be secondary to an inhibitory effect on renin release and that a decrease in the latter could play a role in the depression of plasma aldosterone.