Hemofiltration has been suggested as a new therapeutic tool in refractory heart failure. In this study, 11 patients with primary or ischemic heart disease in New York Heart Association class IV, in whom there was no response to medical treatment, were subjected to hemofiltration. The pathophysiologic adjustments promoted by subtraction of plasma water were investigated, and guidelines for an appropriate use of this procedure in heart failure are provided. Fluid was removed from plasma at a rate of 500 ml/hour until either normalization of the right atrial pressure (which was increased in all cases) was achieved or the hematocrit exceeded 50 percent. According to these criteria, the duration of treatment ranged from four to six hours and the total amount of fluid removed was 2,000 to 3,000 ml. In each case, hemofiltration promoted relief of dyspnea and of clinical and radiographic evidence of lung congestion and pleural effusion, and substantially reduced the dependent edema and abdominal girth. These effects were paralleled by progressive decrease of the right (-70 percent) and left (-45 percent) ventricular filling pressures and of the pulmonary arterial pressure and arteriolar resistance, without significant variations in heart rate, aortic pressure, cardiac index, and systemic vascular resistance. Changes in the right atrial and wedge pulmonary pressures are interpreted as reflecting a combined effect of a decrease in pressure on the outside of the heart due to fluid reabsorption (from lung interstitial spaces and pericardial, pleural and abdominal cavities) and of intravascular volume subtraction. The arterial partial pressure of oxygen was raised, the partial pressure of carbon dioxide and pH were unchanged, and urinary output was substantially enhanced by the procedure. The study indicates that: hemofiltration may be a short-term treatment for refractory cardiac insufficiency with overhydration; a filtration rate of 500 ml/hour is effective and safe; and the central venous pressure may be a reliable guide to volume subtraction.