Background-Patients with chronic severe anaemia often retain salt and water. Fluid retention in these patients is not caused by heart failure and the exact mechanisms remain unclear. This study was designed to examine some of the possible mechanisms. Methods and results-Haemodynamic variables, body fluid compartments, renal function, and plasma hormones were measured in four patients with oedema caused by chronic severe anaemia (mean (SE) haematocrit 13 (1·7)) who had never received any treatment. Cardiac output was increased (6·1 (0·6) 1/min/m2) and right atrial (7·8 (1) mm Hg), mean pulmonary arterial (20·5 (2·0) mm Hg), and mean pulmonary arterial wedge (13 (2·7) mm Hg) pressures were slightly increased. The mean systemic arterial pressure (81 (1·3) mm Hg) and systemic vascular resistance (12·3 (1·1) mm Hg × min × m2/1 were low. There were significant increases in total body water (+ 14%), extracellular volume (+ 32%), plasma volume (+70%), and total body exchangeable sodium (+ 30%). Renal blood flow was moderately decreased (- 46%) and the glomerular filtration rate was slightly reduced ( - 24%). There were significant increases in plasma noradrenaline (2·1-fold), renin activity (15-fold), aldosterone (3·2-fold), growth hormone (6·3-fold), and atrial natriuretic peptide (12-fold). Conclusion-In patients with oedema caused by chronic severe anaemia there is retention of salt and water, reduction of renal blood flow and glomerular filtration rate, and neurohormonal activation similar to that seen in patients with oedema caused by myocardial disease. However, unlike patients with myocardial disease, patients with anaemia have a high cardiac output and a low systemic vascular resistance and blood pressure. It is suggested that the low concentration of haemoglobin in patients with anaemia causes a reduced inhibition of basal endothelium-derived relaxing factor activity and leads to generalised vasodilatation. The consequent low blood pressure may be the stimulus for neurohormonal activation and retention.