The activation of T cells is now thought to require at least two distinct signals. One signal is delivered through the interaction of the antigen-specific T cell receptor with major histocompatibility complex (MHC) molecules and peptide, while the other is received from interactions with less precisely defined accessory or costimulatory molecules. In the absence of this second costimulatory signal, some T cells subsequently become unresponsive to antigenic stimulation. One of the major candidates for providing such a second signal to T cells is the molecule B7 interacting with the T cell glycoprotein CD28. In the present study we have investigated whether B7 is expressed on human T cell lines and clones, since these cells have the capacity to present antigen to each other by expressing MHC class II molecules. Our results demonstrate that B7 can be detected on T cell clones and on repeatedly activated but not freshly isolated peripheral blood T cells. The expression of B7 is dependent on the state of activation of the cells, being maximally expressed shortly after restimulation and becoming undetectable as the cells quiesce. Together, these results suggest that B7 expression may be of importance to T cells, perhaps in the avoidance of anergy.