In order to determine the fine structural differences and labeling by immunoferritin particles of CD4-positive (CD4+) and CD8 positive (CD8+) cells at the ultrastructural level, short term cultured lymphocytes from eight healthy donors seropositive for HTLV-I were examined and virus production was examined in vitro. Sera of eight donors were all positive on the particle agglutination (PA) test, but only of the four of the eight were positive on the immunofluorescence (IF) test. Sera with high titer on the PA test, e. g., above 26, were likely to be positive on the IF test, as well. Ultrastructurally, CD4 + cells were mostly smaller than CD8 + cells, with higher N/C ratio and a heterochromatin-rich nucleus. CD8+ cells were usually more abundant in cytoplasmic organelles than CD4 + cells. Interestingly, in CD4+ cells, two types of surface immunoferritin labeling were observed, light or slightly heavy segmental in pattern, though CD8 + cells were always labeled in dense, heavy segmental fashion, when antibodies were applied to short term cultured fresh lymphocytes. In three of eight cases, only a small number of virus particles were detected in the specimens. These findings demonstrated that labeling of CD4+ and CD8+ cells with each CD4 or CD8 antigen differed, as did the ultrastructural findings for these cells. Further investigation of these differences is needed using other types of markers, such as those for chemokine receptors, and other methods to clearly determine the differences between the two types of lymphocytes in fine structure and how these relate to their functions.