Acquired von Willebrand's disease (AvWD), an adult-onset bleeding diathesis, has most commonly been found in patients with an underlying lymphoproliferative disease or monoclonal gammopathy. Other malignancies, autoimmune diseases, hypothyroidism, and drugs have also been associated with AvWD. We have included an illustrative case history of a patient with a bleeding diathesis consistent with AvWD and a monoclonal gammopathy who required emergent cardiac surgery. Our review of the literature determined that most cases of AvWD are due to a circulating antibody that combines with the high molecular weight multimers (HMWM) of von Willebrand factor (vWF). These vWF multimer-antibody complexes are subsequently cleared from the circulation either by the reticuloendothelial system or by adsorption onto tumor cells. Clearance of the HMWM of vWF thus results in extremely low functional levels and variable antigenic levels. Mixing studies which are traditionally used to diagnose factor inhibitors are useful only if removal of vWF-antibody complexes can be accomplished in vitro. Treatment with intravenous immunoglobulin has recently been shown to be the most effective therapy for patients with an underlying lymphoproliferative disorder or monoclonal gammopathy. This therapeutic strategy is based on the observed immune complex clearance phenomenon that appears to be operative in most cases. Other AvWD-associated diseases require treatment specifically directed at the underlying disorder.