Soluble, T-cell-derived proteins that bind non-MHC-associated (nominal) antigen specifically (TABM) and share V- and C-region epitopes with the T cell receptor for antigen have been shown to modulate T lymphocyte-mediated activity in vitro and in vivo. The occurrence of these (non-immunoglobulin) immunoproteins in serum suggests that they act systemically. In this review, we describe the results of a collaboration between our laboratories and other laboratories in the U.S., Australia and India, on the detection, quantitation and function of human serum TABM in individuals with milk intolerance, infectious diseases such as filariasis and Candida vaginitis, melanoma and in subjects occupationally exposed to solvents. Our results suggest that TABM may be associated with certain symptoms and the modulation of cell-mediated immunity. The immune effects of TABM may be due to the non-covalent association of these immunoproteins with immunoregulatory cytokines such as TGF-β that results in the antigen-specific focusing of cytokines to an antigenic site. Also, the antigen-specific concentration of TGF-β by TABM may, in addition to immune modulation, cause collateral neurological symptoms by the action of this cytokine on sensory nerves. The measurement of serum levels of TABM may indicate immune status and/or pathogenesis.