Antibodies to the ninth component of complement (C9) were found in a patient with hereditary C9 deficiency (C9D) who had received multiple transfusions. The incidence of anti-C9 precipitating antibodies following transfusion was investigated in 63,625 patients treated at Kyushu University Hospital, and 475,886 blood donors at the Fukuoka Red Cross Blood Center were studied to determine the frequency of C9D in Japan. Transfusion reactions in recipients having anti-C9 were also monitored. One hundred and eighty-six subjects (15 patients and 171 donors) with C9D were identified (a prevalence of 0.036%). Four of 15 C9-deficient patients had received transfusions. One of the patients who had received several units of blood within 1 week developed low-titer C9-precipitating antibody. This patient was transfused in the presence of the antibody without evidence of adverse reactions. No precipitating antibody was detected in the remaining three patients who had received several units of blood on a single day. These observations suggest that multiple transfusions may contribute to the development of anti-C9.