The somatomedin activity (SMA) was assayed in 247 plasma samples from 30 patients with moderate or severe injuries. The injury severity score (ISS) was assessed for each patient and ranged from 9 to 50. The plasma SMA was reduced or eliminated within 4 days of injury. The activity then increased in the patients who recovered, normal levels being attained within 1 or 2 weeks of the injury. Five patients had at least one further fall in plasma SMA during treatment. Seven patients died and 4 of these had little or no SMA before death. The magnitude and duration of the depression of SMA after injury correlated both with the ISS and with the probability of mortality. The plasma cortisol concentration was elevated in all but 4 patients within 48 hours of injury. There was no relationship between the plasma SMA and the cortisol concentration. When plasma samples from 10 patients taken soon after injury were mixed with normal human serum, samples from only 1 patient were found to contain an inhibitor(s) of SMA. The reduced plasma SMAs in the remaining patients may have resulted from the impaired production of somatomedins (SM), the degradation of SM, the dilution of circulating SM with transfusion fluids or the binding of SM to damaged tissues.