We report the first case of systemic lupus erythematosus with hyperviscosity syndrome as the presenting manifestation. A polyclonal increase in all immunoglobulins was observed. Ultracentrifuge studies showed 17-19S intermediate immune complexes (IC) composed primarily of autoreactive IgG demonstrated at acid pH. This was confirmed by chromatographic fractionation of sera, since the intermediate IC eluted as did purified heat aggregated IgG. Small amounts of IgM and IgA in the intermediate IC were also demonstrated by more sensitive techniques, i.e., nephelometry, polyacrylamide gel electrophoresis, and electrophoretic blotting. The decrease of serum viscosity was associated with the decrease of circulating IC after plasmapheresis or combined treatment of prednisone and cyclophosphamide. Serum viscosity bore no relationship to the amount of dissociated immunoglobulins.