An example of anti-Cob which caused an acute hemolytic transfusion reaction is reported. Immunohematologic studies showed this antibody to be an IgG immunoglobulin that weakly bound complement and reacted in the antiglobulin phase of the crossmatch. The unit of whole blood implicated in the hemolytic transfusion reaction was from a donor who was phenotyped as Co(a+b+). The patient gave no history of previous transfusions; however, anti-E and anti-c were also present.