Circulating immune complexes were identified in cryoproteins isolated from serial samples of serum from six patients with acute viral hepatitis with and without arthritic symptoms. Cryoprecipitates were analyzed for the presence of hepatitis-B surface antigen (HBsAg) and hepatitis-B surface antibody (anti-HBs) by hemagglutination inhibition and hemagglutination. Complement components were detected by counter electrophoresis, and immunoglobulins were detected by gel diffusion. HBsAg, IgG, and IgM were identified in cryoprecipitates from all hepatitis patients, but were higher in concentration in patients with arthritis. Only cryoprecipitates from hepatitis patients with arthritis contained IgA and complement components C3, C4, and C5 as well as IgG and IgM, which disappear with resolution of the arthritis. The subtypes of IgG in these cryoprecipitates were predominantly the complement-fixing IgG1 and IgG3, HBsAg and anti-HBs were concentrated several-fold in the cryoprecipitates when compared to the serum concentration. Sequential studies in two patients demonstrated that the initial appearance of anti-HBs in the cryoprotein complex was associated with the detection in the complex of IgM suggesting a primary immune response to HBsAg. The C3 activator fragment (C3A) of the properdin complex was found in fresh serum obtained from three hepatitis patients with arthritis and not in uncomplicated hepatitis. The cryoprecipitable immune complexes from patients with arthritis converted C3PA in fresh normal sera to C3A in vitro whereas cryoprotein isolated from patients with uncomplicated hepatitis had no such effect. Thus, the transient appearance of circulating complement-fixing immune complexes in patients with the arthritis of acute hepatitis is associated with activation of both classical and alternate complement pathways and suggests that they play an important role in the pathogenesis of these serum sickness-like extrahepatic symptoms.