We studied the biochemical and the clinical consequences of the application of continuous venovenous hemodiafiltration to the management of acute renal failure in critically ill patients. One hundred consecutive surgical and medical ICU patients with acute renal failure were entered into a prospective clinical study at an intensive care unit of tertiary institution. METHODS included assessment of illness severity by APACHE II score on admission and by organ failure score prior to initiation of renal replacement therapy; treatment of patients with continuous venovenous hemodiafiltration; and measurement of biochemical variables prior to and after therapy. Outcome assessment included incidence of complications, duration of oliguria, duration of intensive care and hospital stays, and survival to hospital discharge. RESULTS included the following: mean patient age was 60.9 years (range 21-81 yr); mean APACHE II score, 28.6 (95% confidence interval; 27.4-29.8); and number of failing organs, mean, 4.1 (95% confidence interval; 3.8-4.4). At commencement of continuous venovenous hemofiltration with dialysis, 79% of patients were receiving inotropic drugs and 72% were septic, and, in 35%, bacteremia or fungemia was demonstrated. Renal replacement therapy was applied for a mean duration of 186.2 hours (95% confidence interval; 149.2-223.7), with a mean hourly net ultrafiltrate production of 621 mL (95% confidence interval; 594-648) and a mean urea clearance of 28.1 mL/min (95% confidence interval; 26.7-29.5). Azotemia was controlled in all patients (plasma urea < 30 mmol/L). During the more than 18,000 hours of treatment, there was no therapy-associated hemodynamic instability. Complications were rare. They included two cases of hemofilter rupture with minor blood loss and a single case of bleeding at the site of the vascular-access catheter. Forty-three patients survived to ICU discharge, and 40 survived to hospital discharge. Continuous venovenous hemodiafiltration is a safe and an effective form of renal replacement therapy in critically ill patients. In such patients, who have a high predicted mortality rate, it was associated with a 40% survival rate. These findings suggests that continuous venovenous hemodiafiltration may be ideally suited to patients with multisystem organ failure with acute renal failure.