Dendritic cells (DC) act as primary antigen-presenting cells and probably initiate T-cell responses via the formation of DC-T-cell clusters. Both DC and T cells express members of the leucocyte common (CD45) family of molecules as major cell membrane proteins. The possibility that the leucocyte common antigens (LCA) play a functional role in the cellular events of a primary T-cell response was tested, by examining the effect of CD45 antibodies on the T-cell proliferative response induced by stimulating with allogeneic DC in the mixed leucocyte reaction (MLR). The presence of individual CD45 monoclonal antibodies during the MLR inhibited T-cell proliferation only weakly, but a mixture of monoclonal antibodies against different epitopes of the LCA had a more profound inhibitory effect. The effect of the CD45 antibodies was maximal during the first 24 hr and preincubation experiments indicated that the major blocking effect occurred at the T-cell level, although some inhibition after preincubation with DC was noted. Purified allogeneic CD8 T-cell responses were more susceptible to inhibition than purified CD4 cell responses, but no difference in the inhibition of the CD45RA (CMRF-11) or CD45RO (UCHL1) LCA-positive T-cell subsets was observed. The presence of CD45 antibodies did not inhibit DC-T-cell clustering but reduced cluster stability, suggesting that certain epitopes of the LCA may be involved in the process of cell adhesion.