Human cytomegalovirus (HCMV) is frequently detected in autoimmune diseases, but its role in such disorders is poorly understood. Herein we describe the case of a young woman who developed generalized Wegener's granulomatosis (WG) after HCMV mononucleosis and urinary tract infection. During mononucleosis, the patient had extraordinarily high plasma levels of proinflammatory cytokines such as interleukin-5 and lymphotoxin alpha, autoantibodies, and a higher blood level of viral DNA than were found in other immunocompetent patients infected with HCMV or healthy controls. Active HCMV replication was detected after the onset of vasculitis, and HCMV genomes or antigens were found in blood, urine, and inflammatory lesions on the kidney. Thus, HCMV may have triggered or exacerbated inflammation and autoimmunity in this case of WG.