We studied basal serum atrial natriuretic peptide (ANP) levels and the response to acute salt loading in rats with different grades of functional renal mass reduction. The six groups of rats studied included 2 controls, i.e. unoperated (n = 12) and sham-operated (n = 24) groups. Each of the 4 experimental groups (n = 24 in each) underwent one of the following procedures: bilateral nephrectomy; unilateral nephrectomy; bilateral ureteral ligation; unilateral ureteral ligation. Basal ANP was assessed in the intact controls and operated groups 4, 8, 16 and 24 h after surgery. In addition, ANP was determined in the sham-operated controls and in the experimental groups 1 h following acute intravenous saline loading performed 4 h after surgery with central venous pressure monitoring. Basal ANP dropped significantly following bilateral nephrectomy but was not significantly altered after unilateral nephrectomy or the two modalities of ureteral ligation. In all 4 experimental groups ANP failed to rise after saline loading. We conclude that substantial renal damage results in early impairment in ANP secretion suggesting the existence of a renal physiological stimulus controlling ANP release by cardiac atria.