The immune systems of patients with HIV infection are characterized by a vigorous turnover of lymphocytes that represents an exaggeration of the normal homeostatic mechanisms controlling lymphocyte growth and death in an attempt to compensate for the destructive forces of the human immunodeficiency virus (HIV). Studies of naive and memory phenotypes of CD4 T lymphocytes; studies of lymphocyte survival and trafficking utilizing genetically marked lymphocytes and: studies of T cell receptor families at the molecular level have consistently led to the same conclusion, namely, that the main source of new CD4 T lymphocytes in patients with HIV infection is through the peripheral expansion of existing cells. This is true whether these expansions are due to the blockade of viral replication with anti-viral agents or through the acceleration of T cell proliferation with interleukin-2 (IL-2). Thus, once one has lost existing elements of the T cell repertoire those elements may be lost forever. These data have profound implications regarding the importance of early intervention in patients with HIV infection.