The biocompatibility and performance of two high flux membranes (modified cellulosic: cellulose-triacetate (CTA), and a synthetic material: polysulphon [PS]) were assessed in 31 stable patients on hemodialysis (HD) in a randomized crossover study. Parameters evaluated included leukocytes, complement activation products C3a and C5a, cytokines, lymphocyte subpopulations, urea, creatinine, phosphate, and beta 2 microglobulin. Considering biocompatibility, the drop in the number of leukocytes was more pronounced during CTA HD compared with PS (p = 0.045), although both were low in comparison with cuprammonium dialysis in the same patients, as observed during a separate study. Both membranes induced a low and transient state of complement activation. Interleukin 1 beta and interleukin 6 could not be detected at all, whereas tumor necrosis factor alpha levels were marginally elevated before and after HD with both membranes. During the first 30 min of HD with either membrane, the numbers of CD8+ cells decreased significantly, resulting in an increase in the CD4/CD8 ratios; in addition, the number of NK cells decreased. Performance, as measured by extraction ratios for small molecular weight solutes and Kt/V urea, was significantly better during CTA dialysis (p < 0.001), but almost similar after correction for membrane surface area. On the basis of these data, it seems justified to conclude that, whereas biocompatibility of the PS dialyzer appeared slightly superior to CTA, performance of both dialyzers was comparable.