We have investigated the role of the CD2 protein in the negative regulation of immune function and report that similar to antigen and anti-CD3, the monoclonal anti-CD2 antibodies (T112 and T113) can induce specific unresponsiveness. Antigen and anti-CD2 tolerogenic signals both down-regulated the phenotypic expression of CD3-Ti. In contrast CD2 surface expression was up-regulated after exposure to peptide and down-regulated after anti-T112 and T113 preincubation. However, in both instances interleukin 2 receptor surface levels were increased. These phenotypic changes could only be partly explained by variations in the levels of the transcripts encoding the CD3-Ti and CD2 molecules.