BACKGROUND: Fresh-frozen plasma (FFP) is widely used in patients with coagulation disorders and simultaneous complement activation. Complement activation in FFP itself is poorly investigated. STUDY DESIGN AND METHODS: The concentration of anaphylatoxins C3a and C5a, the complement precursors C1q and factor B, and complement function were measured in 40 consecutively administered FFP units in two pediatric neonatal intensive care units. In 12 samples, the measurements were also performed after incubation with inulin. RESULTS: In 15 of 40 FFP units, both anaphylatoxin concentrations were below the upper cutoff levels reported for healthy humans (C3a, 500 mu g/L; C5a, 5 mu g/L). Anaphylatoxin levels were higher in FFP units produced by apheresis than in those from blood donation. Complement activation of FFP by inulin increased anaphylatoxin concentration, whereas Clq and factor B levels, and complement function remained unchanged. CONCLUSION: Elevated concentrations of anaphylatoxin are frequently found in FFP units produced by apheresis. Studies are necessary to investigate the masons for complement activation and the possibilities of prevention during apheresis. As the concentrations of complement precursors and complement function did not change with activation in FFP, these studies should include measurement of the anaphylatoxins C3a and C5a.