This study assessed the effects of blunt trauma on host defense, including the early kinetics of skin test anergy (A), depressed polymorphonuclear neutrophil (PMN) function, the duration of these changes, and the effect of the nutritional status of the host upon resolution of these defects. Of 31 patients sustaining blunt trauma six (19%) had normal (N) skin tests with no sepsis or death; 25 (81%) demonstrated skin test A with 20% sepsis and 16% mortality (p< 0.001). The severity of the injury correlated directly with the duration of depressed host defense. Abnormalities of PMN chemotaxis and adherence were detectable within 2 hours of injury and were due to circulating blood factors. No gross abnormalities in serum immunoglobulins or complement levels were detected upon admission. The PMN chemotactic inhibition in the serum of these patients was resolved into at least five components varying in MW from 8,000 to > 400,000 daltons. In 11 patients whose skin test responses returned to N in 19 ± 8.3 days (±SD), albumin dropped 0.46 ± 0.30 gm/dl, arm muscle circumference decreased 2.93 ± 1.69 cm, and creatinine height index dropped 30.1 ± 18% from ideal, during the same interval (p< 0.001). Nonseptic patients (18) were at risk from depressed PMN function 20.6 ± 9.3 days, 74% had central lines, operations were ‘clean,’ and 2.8 blood cultures/patient were drawn with no bacteremias. Septic patients (four) were at risk 53.9 ± 9.5 days, all had central lines, operations were 'clean,' 7.8 blood cultures/patient were drawn with 1.7 bacteremias/patient detected. We conclude that blunt trauma causes an immediate depression of host defense which is mediated by a complex system of serum modulators of neutrophil function. Restoration of these defects follows resolution of trauma rather than the nutritional and catabolic state.