Middle molecules, consisting mostly of peptides and small proteins with molecular weight the range of 500-60,000 Da, accumulate in renal failure and contribute to the uraemic toxic state. Β2-Microglobulin (Β2-MG) with a molecular weight of 11,000 is considered representative of these middle molecules. These solutes are not well cleared by low-fl ux dialysis. High-fl ux dialysis will clear middle molecules, partly by internal fi ltration. This convective component of high-fl ux dialysis can be enhanced in a predictable way by haemodiafi ltration (HDF). The convective and diffusive clearance rates of any middle molecule across any haemodiafi lter can be predicted from known or measurable factors such as its sieving coeffi - cient, bound fraction and molecular weight. The removal of middle molecules is also infl uenced by factors within the patient. Β2-MG is distributed within the extracellular fl uid. During HDF, Β2-MG must transfer into the intravascular compartment across the capillary walls. This transcapillary transfer at a rate of approximately 100 ml/min slows Β2-MG removal from the body. Continuing transfer after the end of a treatment session results in a signifi cant rebound of Β2-MG levels. This intercompartment transfer and its effect on Β2-MG clearance and concentration can be predicted by a 2-compartment model. By extrapolation, the behaviour of other middle molecules can be predicted. The 2-compartment model, which takes non-dialytic Β2-MG clearance at a rate of 3 ml/min and Β2-MG generation at a rate of 0.1 mg/min into account, can predict the effect of any HDF schedule on Β2-MG levels. Lowfl ux dialysis results in a Β2-MG level of around 40 mg/l. Three times weekly, 4-hour HDF can reduce Β2-MG levels to around 20 mg/l. Long (nocturnal) HDF can reduce Β2-MG levels to around 10 mg/l, compared to physiological levels of less than 5 mg/l.