We examined the expression, the signal transduction capacity and mouse IgG-isotype specificity of CD16 on human γδ T cells. CD16 is expressed by the majority of γδ T cells in peripheral blood and by part of the γδ T cell clones. The amount of CD16 expressed on γδ T cell clones varied considerably with passaging of the cells, but was always significantly less than on freshly isolated γδ T cells. Like CD16 on CD3-CD16+ natural killer (NK) cells, CD16 on γδ T cells can act as an activation site triggering cytotoxic activity. CD16+ γδ T cell clones exerted antibody-dependent cellular cytotoxicity (ADCC) which could be blocked by anti-CD16 mAb. ADCC activity of γδ T cell clones was also inhibited by anti-CD3 mAb, suggesting a functional linkage between the CD16 and CD3 activation pathways. MAb directed against CD16 induced lysis of FcγR+ target cells by CD16+ γδ T cell clones. The mouse IgG-isotype specificity of CD16 on γδ T cells was analyzed using isotype switch variants of a murine anti-glycophorin A mAb in EA rosette assays, and was found to be identical to that of CD16 on CD3-CD16+ NK cells, i.e., highest affinity for mIgG2a, intermediate affinity for mIgG2b, and undetectable binding of mIgG1-sensitized erythrocytes. CD16 was partly modulated from the cell surface of both γδ T cells and NK cells after rosette formation with mIgG2a-sensitized erythrocytes, indicating that the rosette formation was indeed mediated via the CD16 molecule. © 1992.