Functions of the CD8 molecule were examined to determine whether CD8 is merely a ligand-binding molecule and/or is involved in signal transduction. Using KT112 (anti-CD8-beta), CD8 was demonstrated to transduce an activation signal leading to cytotoxicity. Conformational changes of the CD8 molecule might be responsible for the activation, because (i) KT15 (anti-monomorphic CD8-alpha), but not antibodies specific for polymorphic CD8-alpha determinants, abrogated KT112 (anti-CD8-beta)-induced cytotoxicity without blocking the binding of KT112, whilst (ii) KT112 (anti-CD8-beta) inhibited KT15 (anti-monomorphic CD8-alpha)-mediated augmentation of proliferation triggered by a V-beta-11-specific antibody without blocking the binding of KT15.