Continuous removal of middle molecules by hemofiltration in patients with acute liver failure. In patients with acute liver failure and hepatic coma, an increase in the abnormal "middle molecules" seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived greater than 3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant. 