In patients with severe aplastic anemia (SAA), lymphocyte subpopulations were examined for the presence of HLA-DR and 2H4 (suppressor/inducer subset) antigen-expressing cells by flow cytometric analysis. Investigations were performed on peripheral blood lymphocytes before and after therapy with antithymocyte globulin (ATG) and methylprednisolone (MP), as well as on bone-marrow lymphocytes before therapy. Before treatment, only the absolute numbers of CD4+ T cells and the CD4+HLA-DR+/CD8+HLA-DR+ activated T cell ratio were significantly decreased (p less than 0.01 and p less than 0.001, respectively). Following successful ATG/MP treatment, a decrease in the CD4+/CD8+ T cell ratio was found. Regarding the suppressor/inducer subset, only absolute numbers of CD4+/2H4+ cells were somewhat higher in treated patients; the percentages were the same in all groups of patients. Studies performed on bone-marrow lymphocytes showed significantly decreased percentages of CD4+ and CD8+ T lymphocytes, which also express HLA-DR antigen. No significant changes in the distribution of activated T cells following ATG/MP therapy were found, suggesting that these cells play no major role in the pathogenesis of the disease.