Studies of the serum of patients with nasopharyngeal carcinoma (NPC) demonstrate increased levels of immunoglobulins (Igs), Epstein-Barr virus (EBV) antibodies, and specific immunosuppressive acute-phase proteins (haptoglobin, alpha 1-acid glycoprotein). Recent correlations of the levels of acute-phase and immune-reactive proteins with tumor extent, immune reactivity, and circulating immune complex (CIC) levels in patients with head and neck squamous carcinoma prompted an investigation of the relationship of CICs to those protein factors characteristically altered in the serum of patients with NPC. In 70 untreated NPC patients and 21 normal participants, levels of CIC, Igs, immune-reactive proteins, and EBV antibody titers were measured and correlations with tumor extent and clinical stage determined. In patients with advanced tumors (stages III and IV), levels of CIC, immunoglobulin A (IgA), immunoglobulin M (IgM), and acute-phase proteins (haptoglobin, alpha 1-acid glycoprotein, alpha 1-antitrypsin) were significantly increased compared to stage I, stage II patients, or normals. In patients with elevated CIC levels, levels of IgA and IgM were significantly increased compared to normals or patients with normal CIC levels. Uniquely, serum IgA levels correlated directly with CIC levels among patients but not controls. EBV antibody titers were increased in the NPC patients and were not significantly related to tumor extent or CIC levels. The immunosuppressive properties of CICs might account, in part, for the immune suppression previously reported in patients with NPC. Thus, the increased levels of CICs demonstrated in these patients provide a rationale for evaluating the effects of removing CICs, since such therapeutic manipulations have been associated with tumor regressions in patients with other tumor types.