a2HS glycoprotein is a normal constituent of plasma. It has a high affinity for hydroxyapatite and is concentrated in bone 100-fold greater than albumin, however its biological function in bone is not known. We have purified a2HS from human plasma and examined it for evidence of chemotactic activity against human peripheral mononuclear cells, polymorphonuclear leucocytes and lymphocytes in Boyden chamber assays. We observed that the protein was chemotactic for mononuclear cells and that maximal cell migration occured when its concentration in the lower compartment of Boyden chambers was lo-'' M. Chemotaxis did not occur in the absence of a concentration gradient. In addition, cell migration was blocked when the cells were preincubated with M a2HS or when the protein was preincubated with rabbit anti-human a2HS glycoprotein IgG. Neither polymorphonuclear leucocytes, which are responsive to a wide range of chemoattractants, or peripheral lymphocytes exhibited directed migration to a2HS in Boyden chamber assays. The glycoprotein appears therefore to act as a chernotaxin directed to monocyte recruitment, and we speculate that the protein may have an important role in monocyte recruitment to bone and possibly their subsequent fusion and differentiation into functional osteoclasts.