Historical accounts have suggested a temporal relationship between famines and epidemics. More recently, careful epidemiologic studies have shown a relationship between nutritional deficiencies and heightened risk of morbidity and mortality due to infectious disease. These observations led to studies that examined the effect of protein-energy malnutrition on immunocompetence. The lymphoid tissues, particularly the thymus, were found to be atrophied. There was a reduction in delayed cutaneous hypersensitivity, fewer T cells, especially T helper cells, decreased thymulin activity, impaired secretory immunoglobulin A antibody response, decreased antibody affinity, reduced concentration and activity of complement components and phagocyte dysfunction. These observations were then applied to the study of individual nutrient deficiencies. The interactions of protein-energy malnutrition and the immune system have generated many practical and clinical applications.