CD68 antigen is expressed by tissue macrophages and cells of myeloid/mononuclear lineage. CD68 is recognized by many monoclonal antibodies (mAbs), including KP1, EMB11, Y1/82A, Y2/131, Ki-M6, and Ki-M7. Using the labeled strept-avidin-biotin (LSAB) immunoperoxidase technique, we examined CD68 antigen expression in human peripheral blood T cells. The anti-CD68 mAbs KP1 and EMB11 stained virtually all fresh isolated gamma/delta T cells and CD3-CD56+ natural killer (NK) cells in a granular cytoplasmic pattern. In contrast, fresh isolated CD4+ and CD8+ T lymphocytes showed no detectable reactivity with these two anti-CD68 mAbs. However, in vitro stimulation with T-cell mitogen or recombinant interleukin-2 (rIL-2) induced expression of CD68 antigen in activated CD4+ and CD8+ T lymphocytes. Similarly, the lymphokine-activated killer (LAK) cells generated after long-term (14 to 21 days) culture of peripheral blood mononuclear cells (PBMC) in rIL-2 also showed strong granular cytoplasmic staining by the anti-CD68 antibodies. This study shows that the CD68 antigen is constitutively expressed in NK cells and gamma/delta T cells and that its expression is strongly induced in activated CD4+ and CD8+ T lymphocytes as well as LAK cells.