The murine T cell clone D10.G4.1 can be induced to proliferate by monoclonal antibodies (mAb) to the T cell receptor (TcR) or to Thy-1 molecules. When cells were stimulated by anti-TcR mAb, a group of 4 proteins (19-25 kDa) was specifically phosphorylated. This effect was completely mimicked by the Ca2+ ionophore A23187, whereas only two of these proteins (19 kDa and 25 kDa) were phosphorylated after cell exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. By contrast, anti-Thy-1 mAb had no effect on the phosphorylation of these proteins, but induced specifically the phosphorylation of a protein of 32 kDa. These results therefore demonstrate that distinct activating pathways in T cells involve the phosphorylation of different proteins, suggesting that the stimulation of protein kinases in T lymphocytes is an early event in cell activation.