In this report, we describe for the first time an epitope common to human myelin basic protein (H.MBP), a structural component of central nervous system myelin, and T lymphocyte CD3, an activation molecule important in signal transduction. This cross-reactive determinant was recognized by a murine mAb WW.B1, which was raised against H.MBP. WW.B1 recognized PBMC and the Jurkat T leukemic cell line, immunoprecipitated both H.MBP and a complex indistinguishable from CD3, and possessed the same biologic properties--induction of T lymphocyte proliferation and inhibition of CTL function--as commercially available anti-CD3 antibodies. It is likely, however, that the epitope recognized by WW.B1 is distinct from those recognized by the anti-CD3 mAb OKT3 and anti-Leu-4. Although the biologic importance of this common determinant awaits further clarification, it is conceivable that autoimmunization to MBP could induce similar immunoregulatory antibody specificities.