The systemic infusion of complement-derived anaphylatoxin ane chemotaxins during hemodialysis results in profound transient neutropenia and may be associated with subtle pulmonary dysfunction. The fact that these potent inflammatory peptides do not usually produce serious ill effects may be due in part to their rapid inactivation by the serum regulatory proteins anaphylatoxin inactivator (AI) and chemotactic factor inactivator (CFI). Accordingly, the authors investigated the effect of hemodialysis on circulating neutrophil counts and serum levels of AI and CFI activity in 10 patients. In all patients, circulating neutrophil counts plummeted by more than 50% within 5 minutes of the onset of dialysis and rose beyond control levels by 1 hour. AI activity significantly fell from 65 +/- 16 mU/ml before dialysis to 18.7 +/- 7.8 mU/ml within 5 minutes of its initiation; levels remained depressed throughout the procedure. In contrast, CFI gradually increased, achieving a level significantly different from the predialysis value by 15 minutes. These events contrasted with the observation that activation of the complement system in vitro results in a significant decline in both CFI and AI activities. We suggest that the maintenance of or increase in CFI activity in patients undergoing hemodialysis enhances the clearance of circulating chemotactins, preventing the persistent activation of neutrophils during the procedure and subsequent organ dysfunction.