Serial serum atrial natriuretic peptide (ANP) determinations were performed in 15 uninephrectomized Charles River rats and in 15 sham-operated control animals during the 60 days following surgery. In a second group of 7 control and 7 uninephrectomized animals housed in metabolism cages, serum ANP, body weight, 24-hour urine volume, osmolality and sodium excretion were serially measured. In a third group of uninephrectomized and control rats the effect of acute salt loading 24 h, 6 and 60 days after surgery on serum ANP was studied. No significant changes in ANP levels were observed during the 60 days following surgery in control animals. In the uninephrectomized animals a sharp drop in basal ANP levels was evident 24 and 48 h after surgery, but increased levels of serum ANP were seen from day 6 to 28. Thereafter ANP returned to baseline levels for the rest of the study period. Urinary sodium excretion decreased in the nephrectomized animals on days 1 and 2 following surgery. No such change was seen in the control animals during the same period. Body weight, 24-hour urine volume and urine osmolality were not statistically different in the nephrectomized vs. control rats at any time and remained constant in each group throughout the experimental period. Central venous pressure (CVP) did not change significantly in both groups 24 h and 6 days following surgery. CVP rose similarly in both groups immediately following saline loading and returned to preload levels 1 h later. Nephrectomized animals showed no change in serum ANP 1 h after saline loading performed 24 h after surgery, while in control animals acute saline load resulted, as expected, in a significant rise in serum ANP. 6 and 60 days following surgery, augmented ANP release 1 h after acute salt loading was evident in both the nephrectomized and control groups. We suggest that some as yet unknown mechanism exists through which the renal mass contributes to the control of ANP secretion by the cardiac atria.