When samples were taken within 2 hr of accidental injury, plasma cortisol levels increased with injury severity score (ISS) in patients with minor and moderate injuries (ISS, 1-12) but decreased at higher ISS. Radioimmunoassay of adrenocorticotrophin (ACTH) showed very variable plasma concentrations at all ISS ranges. Like cortisol, ACTH increased with ISS up to a score of about 13, but it thereafter plateaued, and in patients with severe injuries plasma cortisol fell in relation to ACTH as well as in absolute terms. This suggested that although ACTH secretion was generally far from maximal the relatively low cortisol concentrations in the most severely injured were at least partly due to a poor response of the adrenal cortex to ACTH. In patients who presented late (more than 2 hr after injury) plasma cortisol levels were more variable and more strongly related to ACTH than at shorter times after injury. The variability of cortisol also increased with age. Patients with severe head injuries had cortisol and ACTH concentrations similar to those without head injuries but with a similar ISS from injuries in other parts of the body.