In an attempt to return to normal serum beta 2-microglobulin levels in a group of seven ESRD patients, a programme of daily HF with highly permeable AN69 membranes was undertaken. Pre-HF beta 2-M serum levels stabilized after 4 days at 20 mg/l, only 40% lower than the initial concentration. A total of 985 +/- 20 mg beta 2-M was removed over the week. The beta 2-M release rate averaged 97 micrograms/min with a broad range of values (63-128 micrograms/min). beta 2-M release peaked at 602 micrograms/min 1 h after the end of the HF session before returning to baseline by 12 h post-HF. We conclude that a return to normal blood beta 2-M concentrations in ESRD patients seems quite unrealistic despite a highly intensive extracorporeal therapy. Therefore other therapeutic alternatives have to be designed to prevent or cure beta 2-M amyloidosis.