The generation of compounds such as interleukin 1 (IL-1), tumor necrosis factor alpha (TNFα), and the possible encounter of circulating cells with endotoxin (LPS) have been demonstrated during hemodialysis. All these factors are able to induce the production of IL-6 by human monocytes. Anaphylatoxins can be generated following complement activation by cellulosic membrane dialysis. C5a is known to potentiate the LPS-induced production of IL-1 and TNFα, and we established that recombinant human C5a was able to act synergistically with LPS in the induction of IL-6 by human monocytes. We investigated whether IL-6 could be detected in the serum of long-term hemodialyzed and uremic patients. Using the very sensitive 7TD1 cell line bioassay, we demonstrated that circulating IL-6 activity was present in the serum of all 14 tested patients, whereas it was occasionally present in normal sera. The presence of serum IL-6 was confirmed using an anti-IL-6 antibody and a specific ELISA (109 ± 36 pg/ml). Most patients had a reproducible level of IL-6 activity throughout a period of 10 days. The dialysis session did not significantly modify these levels and patients had similar serum IL-6 activity at the start, during or the at end of the dialysis session. The different parameters of the dialysis session (i.e. standard or filtrated dialyzates, complement-activating or nonactivating membranes) did not significantly influence the levels of IL-6. Elevated levels of IL-6 were also observed in uremic patients compared to normal donors, although significantly lower than in hemodialyzed patients (p = 0.001). Since IL-6 is a hepatocyte-stimulating mediator, we searched for a correlation with C-reactive protein (CRP). Although 4/14 hemodialyzed patients and 5/9 uremic patients had high CRP values, there was no correlation with IL-6 levels. Whether or not the hemodialysis itself or the pathology is responsible of the elevated level of IL-6 is discuss