We have prepared an antiidiotype antibody that specifically reacts with and inactivates a human autoantibody to factor VIII (VIII:C). The antiidiotype specificity of this rabbit antibody was evident in solution, as specific inhibition of anti-VIII:C activity, and in solid-phase studies. The antiidiotype antibody inhibited both plasma anti-VIII:C and Fab' fragments prepared from that plasma's IgG. Although the antibody had a greater inhibitory effect on the anti-VIII:C used for immunization than it did for other anti-VIII:C, partial inhibition was identified with ten of 25 other human anti-VIII:C. The demonstration that antiidiotype antibodies can be prepared to human anti-VIII:C indicates the feasibility of this approach to the immunochemical characterization of human anti-VIII:C inhibitors. Moreover, antiidiotype reagents have a potential role in the treatment of inhibitor patients.