Fulminant gangrene of the fingers, toes and nose developed in a 57-year-old woman with Escherichia coli pneumonia. Cryoglobulinemia was noted, and the cryoglobulin was identified as IgM-IgG with anti-I cold agglutinin activity. The cold agglutinins possessed potent lymphocytotoxic and monocytotoxic activity and weaker granulocytotoxic activity. Treatment with plasmapheresis, steroids and antibiotics led to complete clinical recovery, although amputation of several toes was necessary. The patient died 1 1/2 years later; the main findings at autopsy were chronic and acute pyelonephritis and acute bacterial endocarditis. This seems to be the first case of IgM-IgG cold agglutinemia occurring during the course of E. coli infection and the third case of fulminant gangrene complicating transient cold agglutinemia.