Since some haemophiliacs manifest profound immunodeficiency with no evidence of human immunodeficiency virus type 1 (HIV) infection, we measured the circulating immune complex (CIC) level in sera obtained from haemophiliacs and addressed the question of whether viral infection is associated directly or indirectly with enhanced CIC production. While more than 90% of HIV-positive individuals had a high level of CIC, around 60% of seronegative ones also showed CIC levels comparable to those of seropositive patients. These sera activated fresh complement in vitro. The patients infected with either HIV or Hepatitis C virus (HCV) or both showed higher frequency and concentration of serum CIC than those free of either pathogens. It is worth noting, however, that 64% of patients with no evidence of infection with HIV or HCV produced significant amounts of CIC. Among the infectious viruses examined, parvovirus is considered as one of the pathogens associated with CIC synthesis, since all the haemophiliacs including the HIV-free patients who had been supplied with heated coagulation factors for several years from birth carried antibodies to parvovirus B19. Strikingly, 60% of the children in this category were positive for CIC, suggesting the possible contribution of parvovirus infection to CIC formation.