Idiopathic CD4+ T-lymphocytopenia (ICL) in HIV-seronegative patients is a newly described, rare entity. The common underlying abnormality is a usually stable depletion in CD4+ lymphocytes in patients, some of which have unexplained opportunistic infections. We present a previously unreported condition of an asymptomatic individual with CD4+ T-lymphocytopenia and a selective IgA deficiency. The subject is a 35-year-old healthy white male with a documented 5-year history of low CD4+ T cell counts. He has been repeatedly HIV seronegative and has no risk factors for HIV infection. Data were obtained from several laboratories over a 5-year period and include standard WBC differentials, HIV testing, serum immunoglobulin quantitation, mitogen stimulation assays, diphtheria and tetanus antitoxin titers, and flow cytometric immunophenotyping. The composite results show a subject with a normal white blood cell count, an absolute lymphopenia, a slight granulocytosis, and a selective IgA deficiency. Leukocyte subset analyses show essentially normal B but significantly altered T cell phenotypes. The normal CD4:CD8 ratio shows extreme inversion, primarily due to CD4 T-lymphocytopenia.