Delayed hypersensitivity skin testing was performed on 520 surgical patients. Significantly higher incidences of sepsis and mortality (p less than 0.001) were found in the abnormal patients as compared to normal responders in the preoperative (322 patients), postoperative and post-trauma (115 patients), and nonoperative (83 patients) groups. Sequential testing in individual patients was of even greater prognostic value. Of the 177 patients who either remained normal or whose responses became normal, the sepsis rate was 10.1%, and the mortality rate was 8.4%. However, a sepsis rate of 57.6% and a 78% mortality rate were found in those patients who developed abnormal responses or whose responses did not improve. Cancer and increased age (older than 80 years) did not account for the incidence of anergy and relative anergy. The mortality rate was higher in the cancer group. Anergy and relative anergy were found to be associated with malnutrition, sepsis, shock, and trauma. In the clinical setting, effective treatment of these associated conditions, especially the maintenance of body cell mass by the use of total parenteral nutrition, was associated with reversal of the anergic state and an improved prognosis.