Measurable complement activation resulting in the formation of both C3a and C5a anaphylatoxins was observed in 12 patients undergoing maintenance dialysis treatment with cuprophan hollow fiber dialyzers. Specific radioimmunoassay measurements demonstrated that these patients displayed significantly elevated levels of C3a antigen in the venous (outflow) line of the dialyzer after only 2 min of dialysis. During hemodialysis, venous plasma C3a levels continued to increase and became maximally elevated after 15 min. Thereafter, C3a concentrations gradually declined, suggesting that the rate of complement activation abates with continued cuprophan hemodialysis. Complement activation, as judged by venous plasma C3a levels, was also temporally correlated with hemodialysis leukopenia. The factor believed to be responsible for pulmonary vascular leukosequestration, C5a, could also be detected in venous plasma, but levels of this antigen were not strikingly elevated until the later stages of dialysis. By contrast, six patients dialyzed with polyacrylonitrile dialyzers failed to exhibit hemodialysis leukopenia and displayed only very modest increases in their plasma C3a levels during the initial phases of hemodialysis. These observations provide direct evidence that anaphylatoxin formation during hemodialysis is a transient phenomenon and indicate that the biocompatibility of dialysis membranes, as reflected by their complement activating potential, may be significantly different.