We investigated the effects of different dialysis membranes on the production of beta 2-microglobulin (beta 2m) in peripheral blood mononuclear cell cultures (PBMNC) obtained from hemodialysis patients in a prospective cross-over design study. Chronic dialysis with cuprophane membrane leads to an increase in beta 2m production from 129 +/- 11 ng/ml to 192 +/- 23 ng/ml (P less than 0.002). This increase is reversed by the use of a non-complement activating membrane polymethylmethacrylate. In addition, during chronic dialysis with cuprophane membrane, an increasing proportion of these cells display low beta 2m expression on their surface (from 6.1 +/- 0.8% of PBMNC to 16.9 +/- 3.4%, P less than 0.001), concomitant with the emergence of cells with low density of HLA on their surface (from 4.9 +/- 1.2% of cells to 32.9 +/- 7.8% of cells, P less than 0.001). The total content of cell-associated beta 2m is also decreased in dialysis patients in general, and in particular in patients chronically dialyzed with new cuprophane membrane. These effects can be reproduced by incubation of PBMNC with cuprophane membranes, and with the addition of C5a, IL-1 and TNF in vitro. Thus, chronic dialysis with cuprophane membrane may be a factor in the genesis of high beta 2m levels and causes changes in beta 2m and HLA expression on cell surfaces.