A rapid induction of adhesion to immobilized intercellular adhesion molecule (ICAM)-I occurs when cytotoxic T lymphocytes (CTL) are stimulated with either soluble anti-T cell receptor (TCR) monoclonal antibodies (mAb) or with immobilized alloantigen, and this binding is blocked by the addition of anti-lymphocyte function-associated (LFA)-I mAbs. Requirements for activating LFA-1 adhesion to ICAM-1 are similar to those found for induction of binding to immobilized fibronectin (FN), but distinct from those for activating CD8-mediated adhesion to class I major histocompatibility complex. A distinct role for LFA-1 in co-signaling for TCRdependent degranulation could not be demonstrated. In contrast, both CD8 and the FN-binding integrin provide costimulatory signals for this response. Thus, if co-signaling via LFA-1 occurs, it clearly differs from that provided by CD8 or the FN-binding integrin. On the basis of antibody blocking effects, alloantigen-dependent activation of adhesion to ICAM-1 involves both the TCR and CD8. These results support a view of CTL activation as a cascade of adhesion and signaling events, with different coreceptors making distinct contributions.