T LYMPHOCYTES can be activated by various stimuli directed either against the T-cell antigen receptor-CD3 antigen complex (Ti-CD3) or the CD2 molecule; see ref.1 for a review. Activation signals generated by antigen binding to the antigen-specific α/β heterodimer (Ti) are thought to be transduced via the invariant CD3 γ, ε and δchains, and the associatedζ and η subunits2,3. The physiological role of the interaction of CD2 with its homologous cell-surface associated ligand LFA-34,5remains to be fully elucidated. It has been suggested that CD2 regulates an antigen-independent pathway of activation6or that signals delivered via CD2 are an integral part of the antigen-specific pathway7-10. Several recent studies have indicated a requirement for the Ti-CD3 complex in CD2 signalling. Thus, mutant T-cell lines expressing CD2, but not Ti-CD3, on the cell surface cannot be activated via the CD2 molecules9,10. Functional interaction between the Ti-CD3 complex and the CD2 antigen suggests that these T-lymphocyte cell-surface structures are physically associated. Here we use a digitonin-based solubilization procedure to explore this possibility and show that 40% of the cell-surface CD2 molecules can be specifically co-precipitated in association with the Ti-CD3 complex.