We found a 81-year-old man with Hashimoto's disease and bullous pemphigoid whose activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged. Mixing studies with normal plasma failed to correct APTT and PT, suggesting the presence of circulating inhibitor. The patient's factor V activity was 11% of normal control and was not corrected by mixing with normal plasma, indicating the presence of an inhibitor against factor V. This inhibitory activity was observed up to 32 times dilution of the patient's plasma. The inhibitor activity against factor V was not detected in the fraction of the patient's plasma that passed through Protein A Sepharose, but detected in the elution with glycine-HCl buffer. Furthermore, using SDS-PAGE and immunoblotting method, purified IgG from the patient's plasma reacted with a protein with molecular weight (74KD) equivalent to F1F2 of factor Va which was activated by thrombin. The inhibitory activity was associated with IgG4 subclass. These data indicate that the inhibitor was IgG antibody which inhibit F1F2 of factor V. Autoimmune mechanism was strongly suggested for the development of the antibody.