β(2)-Microglobulin is a low molecular weight protein with sequence homology to immunoglobulins. As a portion of the HLA complex this protein is an important cell-surface structure. Under normal conditions β(2)-microglobulin is synthesized and shed by many cells,particularly lymphocytes, and is detectable in the circulation of normal individuals. Because of its small size it is normally filtered readily at the glomerulus and is catabolized by proximal tubular cells of the kidney. Impaired renal function and hyperproduction of β(2)-microglobulin are both associated with increased serum levels. A function for β(2)-microglobulin as a modulator of lymphocyte surface and as a potential regulator of the immune system is proposed.