We have previously identified and cloned BST-1 as a molecule which is overexpressed on the bone marrow stromal cell lines derived from patients with rheumatoid arthritis and which has the ability to support the pre-B cell growth. BST-1 is a glycosylphosphatidylinositol-anchored ectoenzyme having ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities. In this report, we demonstrate that human BST-1 was expressed on monocytes, granulocytes in the peripheral blood of healthy donors, and macrophages matured in vitro. Cross-linking of BST-1 with a polyclonal anti-BST-1 antibody induced tyrosine phosphorylation of a 130-kDa protein (p130) in the human myeloid cell lines U937 and THP-1. Cross-linking of BST-1 overexpressed on a transfectant induced tyrosine phosphorylation of p130, dephosphorylation of the 100-kDa protein, and growth inhibition. These results suggest that BST-1 can deliver signals into cells and function as a receptor.