We analyzed CD8+ T cell receptor (TCR) gamma/delta+ (delta-TCS-1 reactive) cell clones expressing the 55-kD gamma chain for their susceptibility to triggering by monoclonal antibodies (mAbs) specific for TCR or CD3 molecules. Clones were derived by limiting dilution from CD3+, WT31- FACS-purified peripheral blood populations or CD4-CD8- thymocytes (a fraction of the latter cells expressing de novo CD8 surface antigen upon culture in IL-2). Clones were screened according to their reactivity with both anti-CD8 and delta-TCS-1 mAbs. Analysis of CD3-associated molecules immunoprecipitated by anti-Leu-4 (anti-CD3) mAb under conditions which preserve the CD3/TCR association (1% digitonin) showed a predominant 55-60-kD molecule both under reducing and non-reducing conditions. All clones expressing the delta-TCS-1+ CD8+ surface phenotype derived from either thymus or peripheral blood lysed the Fc gamma receptor-bearing P815 target cells in the presence of anti-CD3 mAb. On the other hand, delta-TCS-1 mAb was poorly efficient in triggering the lytic machinery of these clones, while it induced target cell lysis by delta-TCS-1+ CD8- clones.