In human T lymphocytes the antigen receptor (Ti) is associated non-covalently on the cell surface with the invariant T3 antigen which comprises 3 chains: two glycosylated polypeptides of relative molecular mass 26,000 (Mr26K) and 21K (γ and δ) and one non-N-glycosylated polypeptide of Mr 19K (ε)1-7. The proposed function of T3 is to transduce the activation signals delivered via the antigen receptor8-13. Recently we have shown that phorbol esters, which stimulate protein kinase C, can induce phosphorylation of the γ subunit of the T3 antigen14,15. But the critical question is whether T3 phosphorylation occurs as a normal consequence of immune activation of T lymphocytes. In this respect, it has been shown that immune stimulation of murine T cells results in phosphorylation of Ti-associated polypeptides that may be the functional analogues of the human T3 antigen16,17. We have therefore monitored T3 phosphorylation after exposure of human T cells to antigen or phytohaemagglutinin (PHA). The data show that both stimuli initiate phosphorylation of the γ subunit of the T3 antigen which indicates that T3 phosphorylation is a physiological response to immune activation.