Though the functional roles of human CD2 are well characterized, murine studies have been lacking until very recent years. Our previous work showed that a mAb against the T11(1)-like domain of CD2 clearly inhibited T cell proliferation induced by mitogenic and allo-antigenic stimuli, but the degree of inhibition was much smaller than had been demonstrated in the human system. In the present study, we observed functional aspects of murine CD2 on CD4+ T cell clones. It was shown that all T cell clones tested were CD2-positive, and that proliferation induced by APC + Ag was inhibited by anti-CD2 mAb. The maximum inhibition was also partial (40-60% inhibition) but CD2-mediated inhibition was observed even at concentrations as low as 0.2 microgram/ml. In contrast to the APC + Ag stimulation, the proliferation induced by lymphokines or immobilized anti-CD3 mAb was not inhibited at all. Taken together, these findings indicate that: (1) CD2 is also involved in the interaction between HTL and APC in murine system; but (2) perturbation of murine CD2 does not influence TCD/CD3- and lymphokine-mediated signal transduction.