Polymorphonuclear neutrophils were isolated from patients with burn injury and random mobility, chemotaxis in response to C5adesArg (as agarose-activated control serum) and to N-formyl-methionyl-leucyl-phenylalanine (F-Met-Leu-Phe) were assessed. For a group of eight patients identified as not experiencing systemic infection, all three neutrophil migratory functions were observed to fall below control levels, beginning 4 to 6 days following burn injury, and to return to control levels after 21 to 30 days of hospitalization. Over this time the chemotactic differential (distance chemotactic migration-distance random migration) for F-Met-Leu-Phe remained positive, while the chemotactic differential for activated serum became nil after postburn day 4. This temporal, specific loss of a chemotactic response to activated serum was associated with rises in immunoreactive plasma C3a and C5a. This pattern of loss of chemotactic function was associated with a selective loss of C5a but not F-Met-Leu-Phe binding activity. These results demonstrate that burn injury can alter neutrophil migratory functions generally, and specifically depress chemotactic responsiveness to activated serum. The mechanism of the latter phenomenon appears to be related to desensitization of circulating neutrophils to C5a due to complement activation.