alpha 1-Acid glycoprotein is an acute-phase reactant that becomes markedly elevated in serum during inflammation and has an immunosuppressive effect on lymphocyte functions. Patients with collagen diseases had significant increases of alpha 1-acid glycoprotein in their serum and on the surface of peripheral leukocytes compared with controls. The levels from patients with rheumatoid arthritis were higher than those from patients with systemic lupus erythematosus, mixed connective tissue disease, and Behçet's disease. In patients with rheumatoid arthritis, the value of serum alpha 1-acid glycoprotein correlated with disease activity. Among leukocyte subpopulations, monocytes showed more alpha 1-acid glycoprotein on their surface than polymorphonuclear leukocytes and lymphocytes. The cell surface expression of alpha 1-acid glycoprotein on cultured monocytes surface peaked after 48 h. Interleukin-1 beta and tumor necrosis factor-alpha stimulated the production of alpha 1-acid glycoprotein RNA message in peripheral blood mononuclear cells over 18-24 h during cell culture. The results show that serum alpha 1-acid glycoprotein reflects systemic disease activity in rheumatoid arthritis. Furthermore, monocytes may serve as a source of production of alpha 1-acid glycoprotein.