This study was designed to investigate the antigenic cross-reaction which occurs in the macrophage electrophoretic mobility (MEM) assay for lymphocyte sensitiza-tion between encephalitogenic basic protein of myelin (EF), a tumour-specific protein (CaBP), an acid-extractable normal membrane protein (AEMP) and the purified protein derivative of Mycobacterium tuberculosis (PPD). Lymphocytes from multiple sclerosis (MS) and cancer patients have been studied. Cellular affinity chromatography has been used to deplete lymphocyte populations specifically of sensitivity to EF or PPD. Subsequent measurement of the reactivity in the MEM test to the other antigens indicated that: (1) removal of EF sensitized cells was accompanied by a similar reduction in sensitivity to CaBP, AEMP and PPD; (2) removal of PPD sensitized cells gave a similar reduction in sensitivity to EF, but less marked for CaBP and AEMP. This is interpreted as evidence for a sharing of antigenic determinants among these proteins.