A majority (42/62) of TCR2+ interleukin 2-dependent human T lymphocyte clones was found concordantly to express not only the CD28 co-receptor structure at the cell surface but also its ligand B7. Interactions between CD28 and B7 can have important consequences for T cell activation, particularly in providing "signal 2" to prevent the induction of anergy caused by stimulation via the antigen receptor only ("signal 1"). However, despite the expression of co-receptor and ligand on the same cell surface, it remained possible to induce hyporesponsiveness in T cell clones either when using CD3 antibodies to deliver signal 1 or when using other T cell clones as stimulators. Thus, the potential for intraclonal autostimulation via CD28/B7 is apparently insufficient to prevent downregulation of responsiveness in these two systems.