T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4+-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. Feline immunodeficiency virus (FIV), first isolated in California (10), is a typical lentivirus that replicates preferably in feline T-lymphoblastoid cells and is structurally similar to human immunodeficiency virus (HIV). Experimental infection of cats induces transient fever, neutropenia, and lymphadenopathy. Following recovery from the initial phase, cats become lifelong carriers of the virus. One year or more after natural infection, cats may develop a terminal AIDS-like phase (12). Hematologic manifestations of FIV infection, including anemia, lymphopenia, neutropenia, and thrombocytopenia, as well as hyperplasia of individual cell lineages and dysmorphic features in bone marrow, are also similar to those in HIV-seropositive humans (14). Strong similarities between FIV infection and the human AIDS complex have been shown, not only in virus structure and clinical symptoms but also in epidemiological manifestations (12, 15). The human counterpart, HIV, is known to infect predominantly CD4+ T-helper lymphocytes and cells of the monocyte-macrophage lineage (3, 8; for a review, see reference 13). Gradual reduction in both the percentage and the absolute number of CD4+ T cells is one of the most striking immunological consequences of HIV infection. Recently, monoclonal antibodies (MAb) against cat CD4 (1) and CD8 (7) homologs have been developed. We have examined peripheral blood lymphocytes from FIV-positive domestic cats with naturally acquired infection (as judged by seroconversion) by using these anti-CD4 and anti-CD8 MAb. We found a variable reduction of CD4+ lymphocytes and an increased proportion of CD8+ lymphocytes in these cats, as already described in a brief report on 20 FIV-seropositive cats (5). MATERIALS AND METHODS Animals. Fifty-seven domestic cats found to be spontane