Serum levels of pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) in patients with hepatitis B virus (HBV) infection were compared with those of healthy male subjects used as controls by a competitive enzyme-linked immunosorbent assay (ELISA). Assay parameters were optimized, and minimal detectable concentration was 100 ng/ml. The alpha 2-PAG levels in 22/26 acute HBV patients showed a very significant statistical difference when compared with controls (x2 = 19.93, p less than 0.0005). On the other hand, 8/8 chronic persistent HBV patients showed high levels with a range between 51 to 200 ug/ml (x2 = 18.16, p less than 0.0005). There was no significant difference between asymptomatic HBsAg carriers and controls. Although alpha 2-PAG apparently exhibits immunosuppressive properties similar to other factors present in HBV infection, follow-up studies are needed to elucidate its role in the natural evolution of this disease.