We aimed to study the biochemical consequences of T-cell activation via the CD2 antigen in mouse T cells. The lack of stimulatory monoclonal antibodies against the mouse CD2 antigen led us to analyse this problem in transgenic mice carrying and expressing the human CD2 gene. Monoclonal antibodies to the human CD2 antigen that were mitogenic for human T cells induced proliferation of mouse T cells from the CD2 transgenic mice. Stimulation was accompanied by rapid phosphorylation of the murine CD3 gamma chain and T-cell receptor zeta chain. These results demonstrate that the human CD2 antigen is functional in the CD2 transgenic mice and indicate a considerable conservation of the signal transducing processes and also the activation mechanisms between mouse and man.