alpha 1-Acid glycoprotein (AG), a serum component elevated during acute inflammation, has been implicated in the suppression of various immunological responses. Pretreatment of lymphoid cells with AG at a concentration commonly found in patients with acute inflammation results in the inhibition of mitogen induced lymphoproliferation as well as capping of concanavalin A (Con A) receptors and surface immunoglobulin (sIg) on the lymphoid cell surface. In order to determine a potential interaction of AG with the lipid bilayer we examined the effects of purified AG on synthetic phosphatidyl choline vesicles. AG displaces 1-anilino-8-naphthalene sulphonate (ANS), an anionic surface probe from these vesicles yet is unable to perturb the binding of N-phenyl-1-naphthalamine (NPN), a hydrophobic probe of the membrane interior. The non-immunosuppressive asialo-derivative of AG is incapable of displacing ANS from the vesicles. The interaction of AG with the membrane may partially involve electrostatic forces mediated by sialic acid and/or steric hindrance of receptor mobility. The results suggest that AG has the capacity to perturb the lymphoid cell surface and interfere with events required for lymphocyte proliferation.