The detection of anergy or relative anergy by delayed hypersensitivity skin tests was predictive of infection and related mortality in 354 surgical patients. Cancer or advanced age alone did not account for the increased morbidity and mortality seen in this study. Altered delayed hypersensitivity response is a reflection of abnormalities in cell-mediated immunity and possibly humoral or phagocytic defects, or both. Skin testing is of value to the clinical surgeon both in identifying the population at risk and in monitoring the immune response to therapy in the seriously ill patient. Failure to improve skin-test response may indicate underlying infection or malnutrition, which, if untreated, results in a high mortality.