Haff disease is a syndrome of unexplained rhabdomyolysis following consumption of certain types of fish; it is caused by an unidentified toxin. Rhabdomyolysis is a clinical syndrome caused by injury to skeletal muscle that results in release of muscle cell contents into the circulation. In 1997, six cases of Haff disease were identified in the United States (four in California and two in Missouri) among persons who ate buffalo fish (Ictiobus cyprinellus), a bottom-feeding species found mostly in the Mississippi River or its tributaries. This report summarizes the investigation of these cases.