Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.