The expression of the CD11b antigen and the presence of the S-100 (and, specifically, its beta subunit) protein within the T4- subpopulation of normal human peripheral blood lymphocytes were investigated by panning techniques, immunofluorescence analysis and immunoelectronmicroscopy. Both antigens are known to be absent in the T4+ lymphocytes. However, CD11b+ T lymphocytes represented about 30% of the T4- population; a part of them (over 1/3) belonged to and completely filled up the T4- T8- subpopulation, whereas the remaining part (almost 2/3) shared the T8 positivity. Interestingly, S-100+ T lymphocytes, which always were CD11b+ too, represented about one half of the CD11b+ T cells, but were excluded from the T4- T8- CD11b+ subpopulation, whereas they represented up to 80% of the T4- T8+ CD11b+ subset. Such findings demonstrate that the S-100+ T lymphocytes are exclusively restricted to a discrete T cell compartment which shows the T8+ CD11b+ immunophenotype. Since such T8+ CD11b+ cells had been shown to possess suppressive capabilities, we herein propose that S-100+ lymphocytes might to some extent modulate the immune responses. However, the exact functional significance of the S-100 protein still remains unknown.