Malnutrition produces atrophy of lymphoid organs and impaired function leading to susceptibility to environmental pathogens, viral reactivation, and development of opportunistic infections. Key aspects of nutrient modulation of immune response are related to micronutrient interactions that are often deficient in generalized infections, in chronic illness, during parenteral nutrition, and in the very young or elderly. Malnutrition is closely associated with mucosal atrophy and poor intestinal absorption. Although immune response to gastrointestinal microflora is usually considered in defensive terms, it now seems likely that an important consequence of this interaction is the production of growth factors, cytokines, and regulatory molecules that selectively control regional immune function. Malnutrition may directly affect cytokine production and cytokines produced in response to infection, interleukin-1, interleukin-6, and tumor necrosis factor can be a direct cause of malnutrition and wasting. Malnutrition is an important factor in many infections, including AIDS because cytokine network interactions critical to host defense may be altered by nutrient status. In addition, current studies suggest that cytokine patterns thought to mediate host defense in peripheral blood are characteristic of an inflammatory response in the gastrointestinal tract and therefore may precipitate altered nutrient metabolism, potentially leading to malnutrition and impaired host defense.