β<sub>2</sub>-Microglobulin (β2M) plasma levels and levels of a second low-molecular-weight protein (myoglobin) were studied during a 2- to 4-hour sham dialysis period (no dialysate flow, no weight loss) and during a 4- to 5-hour hemodialysis (HD) with a Cuprophan® capillary dialyzer. While no rise of the β2M or myoglobin levels occurred during sham dialysis, a rise of 22.1 ± (SD)8.5% (β2M) or 19.9 ± 12.1% (myoglobin) was seen during regular HD. The increases of both molecules showed a significant correlation (r = 0.44; p < 0.03). Both rises could not be completely abolished using correction factors for hemoconcentration. The rises occurred irrespectively of the dialysate buffer. The results suggest that neither the Cuprophan membrane nor the extracorporeal circuit were responsible for the rise of both molecules during HD. It seems more likely that changes of the extracellular volume and extra- to intracellular water shifts are involved and account for the majority of the rise. However, the possibility of minor increase in the extracellular mass of β2M or myoglobin cannot be excluded completely.