Hyperviscosity syndrome is clinically manifested by oronasal bleeding, retinal hemorrhages, and variable neurological symptoms. It occurs when resistance to flow of blood increases sharply, resulting in impaired transit through the microcirculatory system. The most common cause of hyperviscosity is increased concentrations of gamma globulins, either monoclonal in malignant disease or polyclonal, usually seen with rheumatic disorders. Increased numbers of red blood cells, as in polycythemia vera, can result in viscous blood. Extreme increases in concentrations of mature and immature white blood cells can also produce hyperviscosity. Treatment with plasma exchange is required when the clinical syndrome is symptomatic. Although plasma exchange is not a completely benign procedure, it represents the most effective method of controlling hyperviscosity.