A number of non-human-mu eiencvirus (HIV) type 1 disorders are associated with CD4+ T-cell deficiency and dysfunction. However, the etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains unclear. Human in sternal retroviral (HICRV) particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from a patient with severe CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally, the HICRV is distinct from HIV-1i, HIV-2, human T-lymphotropic virus (HITLV) type I, and HTLV-II. Supernatants of activated mononuclear cells showed ificant reverse trunscriptase activity that was predominantly Mn2+ dependent. The patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-i proviruses as demonstrated by the lack of amplification by PCR. Also, the patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-iH and for HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV as demonstrated by Western blot. Similar HICRV particles were detected in a lymphoblastoid cell line exposed to mononuclear cells from the patient's daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1, HIV-2, HTLV-I, and HTLV-U.Human retroviruses are associated with several human diseases that involve disturbances of the growth of CD41 T lymphocytes (1). Human T-lymphotropic virus (HTLV) type I is associated with malignant expansion of CD41 T cells (2), whereas human immunodeficiency virus (HIV) type 1 is associated with depletion of CD41 T cells, resulting in AIDS (3-5). Recently, a human intracisternal A-type retroviral particle was isolated from lymphoblastoid cells exposed to homogenates of salivary gland from Sjogren syndrome (6). The latter virus was antigenically related to HIV-1 p24. No relationship to CD4+ T-cell deficiency was reported. A number of non-HIV-1 disease states are associated with CD4+ T-cell deficiency (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) Coculture of Patient's MNC with H9 Cells and MNC from Controls. MNC (2 X 106 per ml) from the patient (no. 200) were suspended in RPMI 1640 supplemented with penicillin (100 units/ml), streptomycin (100 pg/ml), 2 mM L-glutamine, and 10% heat-inactivated fetal calf serum, hereafter termed culture medium, and cultured with phytohemagglutinin (PHA) P at 10 pg/mi for 72 hr at 370C in a 5% C02/95% air atmosphere. The medium was then changed, and cells were resuspended in culture medium containing rIL-2 at 10 units/ml. At day 7, cells were cocultured with H9 cells or MNC from a healthy control that were preactivated with PHA for 3 days, at a ratio of 1:3 (patient/H9 MNC or patient/normal control MNC). The culture medium was changed every 3 days, and cells were examined for syncytia formation and cell viability. After