The effect that chronic subcutaneous infusion of alpha- and beta-adrenergic and cholinergic agonists on plasma and atrial ANF was investigated. Isoproterenol, a beta-adrenergic agonist, and carbachol, a cholinergic agonist produced a 3-fold increase in plasma ANF levels which were constant until the end of the infusion period. An increased natriuresis was observed in the same groups which was positively correlated with plasma ANF. No differences were observed in atrial content of ANF between the experimental groups. A sharp post-surgery decline in plasma ANF was observed in control, phenylephrine and epinephrine-treated groups which was maintained during the observation period of five days. This suggests that the rise in plasma ANF induced by isoproterenol and carbachol may be secondary to hemodynamic changes and not to direct receptor stimulation, and may play a role in the observed natriuresis. It is also suggested that the depression of plasma ANF may contribute to the well known post-surgery sodium retention.