Skin tests (ST) in 1332 patients are associated with increased morbidity from sepsis. Patients with normal skin tests had a 7% major sepsis rate and 2% mortality rate. Thirty-six per cent of anergic (A) patients and 21% of relatively anergic (RA) patients died; 52% of A patients and 34% of RA patients had sepsis. These data include all patients studied and represent their worst skin test. Two studies were done. The first was a retrospective evaluation of effect of surgery upon 49 anergic patients with biliary tract disease, colon cancer, bowel obstruction, hypovolemia and visceral abscesses. The patients did not receive total parenteral nutrition (TPN). The data show that surgery without TPN can reverse the anergic state and did so in 84% of patients reported. The second study was a prospective, double-blind, randomized trial of the effect of levamisole on skin tests, neutrophil chemotaxis (CTX), sepsis and mortality in 39 preoperative anergic patients. Major sepsis was significantly increased in placebo group (p < 0.05). Mortality, minor sepsis, restoration of skin tests and chemotaxis were somewhat better in levamisole patients but not statistically so. These studies show that in addition to TPN, surgery and inimunorestorative drugs are viable approaches to the management of selected anergic patients.