It has been known for many years that the complement system is activated during extracorporeal plasma purification (ECCP) therapy. In a previous study, we showed that high concentrations of complement activation products (CAPs) are returned to the patient during immunoadsorption treatment. In the present study, we investigated the question of where complement activation takes place with different forms of ECPP equipments as well as the fate of the CAPs. Eleven patients (8 men and 3 women), mean age 52 +/- 18 years, were included in the study. They were treated either with plasmapheresis (PP), immunoadsorption, bilirubin adsorption, or low density lipoprotein (LDL) apheresis. It was found that during all ECPP treatments and after the plasma separation filter, the plasma concentrations of CAPs were increased, and that high concentrations of CAPs were returned to the patients, except with PP. The plasma levels of individual CAPs varied between different types of ECPP. These variations were due to several factors: (1) complement activation (CA) on the plasma separator and a secondary device, e.g., column or membrane; (2) adsorption of specific CAPs to separation columns; and (3) reduction of CAPs due to separation and waste. Since CAPs have inflammatory and immunological effects, it is possible that high serum concentration of CAPs in the treated patients may influence the clinical outcome of the treatment. In conclusion, complement activation is a fact that should not be ignored during performance of any form of an ECPP. It is the plasma separator that plays a key role in the process of complement activation. Different ECPP treatments may have different effects regarding the levels of individual CAPs.