Congenital and acquired states of immunodeficiency have long been associated with an increased incidence of malignant lymphoma. An increased incidence of non-Hodgkin's lymphomas was recognized early in the epidemic immunodeficiency state associated with the human immunodeficiency virus (HIV) infection AIDS. Although the precise etiologic mechanism of these lymphomas remains speculative, the presence of Epstein-Barr viral proteins or sequences and characteristic chromosomal translocations giving rise to altered expression of the c-myc oncogene have frequently been observed. It has been suggested that HIV infection leading to disordered T-lymphocyte function (possibly in conjunction with Epstein-Barr infection) leads to the emergence of polyclonal populations of stimulated B lymphocytes. These cells, which undergo physiologic immunoglobulin gene rearrangement, may provide the background for the occurrence of characteristic chromosomal translocations that lead to the emergence of malignant lymphomas. These lymphomas tend to present clinically with high-grade histopathologic subtype, advanced stage, and a propensity for the involvement of otherwise unusual extranodal sites, including the central nervous system. The experience with therapy for HIV-associated lymphomas has indicated that highly aggressive, dose-intensive chemotherapy regimens may be associated with inferior results. More recent regimens have stressed less myelosuppressive therapy combined with prophylaxis for central nervous system disease and pneumocystis infection. The dominant prognostic factors in the HIV-associated lymphomas appear to be primarily related to the underlying HIV infection and include total CD4 lymphocyte count, performance status, and prior AIDS diagnosis.