Coombs-positive anemia developed in cats inoculated with Haemobartonella felis. Cold agglutinins were detected in serum during the acute stage of the disease when anemia was present. The cold agglutinating activity was associated with IgM, was demonstrated at 4 C, and was abolished by treatment of sera with 2-mercaptoethanol. At 4 C, the sera from infected cats agglutinated or lysed parasitized autologous erythrocytes or normal erythrocytes pretreated with neuraminidase. These data indicate that cold agglutinins are associated with haemobartonellosis and suggest that immunologic responses to erythrocytic antigens have a role in the anemia.