Therapeutic factor-VIII concentrates were found to have factor VIII-related antigen (FVIIIRAg) with an electrophoretic mobility faster than that of plasma using two-dimensional crossed immunoelectrophoresis. Immediately after infusion of factor-VIII concentrates into patients, the electrophoretic mobility of FVIIIRAg in the patients' plasmas was increased to that of the antigen in the infused concentrates. Two hours after infusion, a proportion of the antigen had an electrophoretic mobility intermediate between that of the pre-infusion antigen and that of the concentrate antigen, and by 24 h after infusion the reversion of electrophoretic mobility to pre-infusion values was complete. The return of electrophoretic mobility to normal did not occur in vitro after 24 h. In vitro mixing experiments between pre-infusion plasma and concentrate resulted in antigen with a range of intermediate mobilities which were related to the relative proportions of slow and fast antigen in the mixture. In vitro mixing experiments with slow and fast antigen separated from intermediate purity factor VIII concentrate by agarose gel filtration resulted in the formation of a relatively large proportion of antigen with intermediate electrophoretic mobility. The most reasonable interpretation of the results is the formation of hybrids between the two electrophoretically different populations of antigen. This implies that VIIIRAg normally exists in a polymeric form which can spontaneously dissociate into the exist in equilibrium with a pool of partially and/or completely dissociated subunits.