The progressive decline in the number and function of circulating CD4+ T lymphocytes remains the most characteristic immunologic abnormality found in persons infected with HIV. With the CD4+ cell as the central element in the immunologic cascade of events involved in antigen recognition and host defense, loss of normal CD4 number and function results in impairment of many immune functions that require induction signals by CD4 lymphocytes, including CD8 function, B lymphocyte production of immunoglobulin, NK cell function, and monocyte/macrophage function. Although CD4 cell depletion is a major factor in the pathogenesis of HIV infection, immunologic abnormalities such as impairment of responses to soluble protein antigens appear even before detectable loss of circulating CD4 cells. Progression of clinical disease occurs despite the development of antibodies to HIV proteins. Cellular immune responses have been described in a limited number of individuals, but their exact role is not yet understood. Delineation of the precise nature of the immunologic defects in HIV infection should provide the basis for the continued development of better therapeutic strategies.