The term cryoglobulinemia refers to the presence in the serum of proteins that precipitate at temperatures below 37 degrees C and redissolve on rewarming. The cryoglobulins can be divided into three categories: monoclonal, mixed, and polyclonal. Hyperviscosity syndrome is much more common in monoclonal than in mixed or polyclonal cryoglobulinemia. The clinical manifestations of cryoglobulinemia depend on the underlying disease and may involve various organs or systems. Mixed cryoglobulinemia (MC) is dominated by a vasculitic process, and the clinical manifestations can range from mild to life threatening in their severity. Another common feature of this disorder is the presence of a benign smoldering lymphoproliferative process that can evolve (in a limited number of cases) into non-Hodgkin's lymphoma. The elective treatment for hyperviscosity syndrome, whether associated with monoclonal, mixed, or polyclonal cryoglobulinemia, is plasma exchange. In monoclonal cryoglobulinemia, this procedure seems to act by removing large amounts of abnormal proteins, but its mechanism in MC is far from clear. Here it is possible that qualitative and quantitative variations in the circulating cryoglobulins, as well as hemodynamic changes, are at play. This article will focus on the hyperviscosity syndrome in cryoglobulinemia, beginning with a discussion of its clinical features and then examining the role of hemorheological parameters in the condition.