Eleven patients on chronic maintenance dialysis were investigated before and after intravenous bolus injection of atrial natriuretic peptide (2 μg/kg body weight). Mean blood pressure was reduced to the same extent in the uraemic patients as in 11 healthy subjects, with a nadir 3 min after the atrial natriuretic peptide injection at which time mean blood pressure was reduced by 13% (median) in the uraemic patients and 11% in the healthy subjects. Basal plasma atrial natriuretic peptide and guanosine 3':5'cyclic monophosphate levels were higher in the uraemic patients than in the healthy subjects, but guanosine 3':5'-cyclic monophosphate increased markedly in both groups after atrial natriuretic peptide injection. Using changes in γ-emission from blood after previous labelling of erythrocytes with 51Cr, and changes in packed cell volume, haemoglobin and erythrocyte count, a reversible shift of fluid from the intravascular phase was demonstrated in the uraemic subjects. The blood volume was maximally reduced by 6% (median) of initial blood volume at 30 min after atrial natriuretic peptide injection. Correlation analyses gave no evidence of a causal relationship between the changes in mean blood pressure and changes in blood volume, angiotensin II, aldosterone or arginine vasopressin after atrial natriuretic peptide injection. It is concluded that a pharmacological dose of atrial natriuretic peptide reduces blood pressure in uraemic patients on maintenance dialysis to the same extent as in healthy subjects. The blood-pressure-reducing effect of atrial natriuretic peptides does not seem to be mediated by its diuretic effect or ability to displace fluid from plasma to the interstitial fluid compartment.