Induction of immune tolerance in patients with severe hemophilia A and inhibitors to factor VIII was attempted by daily infusion of 50 U of factor VIII per kilogram of body weight without adjunctive immunosuppressive drugs. Modest initial anamnestic elevation of inhibitor levels occurred in six patients within the first month of therapy; inhibitor levels then fell sharply. The other six patients had no increase in inhibitor levels while on the study protocol. Inhibitors became undetectable within one to ten months in nine of the patients; they now receive smaller and less frequent infusions of factor VIII to maintain suppression. Inhibitors were not eradicated in three patients, who had the highest baseline and historic inhibitor levels. Ten patients gave consent for human immunodeficiency virus (HIV) testing; three had no antibody to HIV at the outset. Two of these patients seroconverted while on the protocol, one of whom had received only donor-screened, heat-treated factor VIII. Thus, the benefits of inhibitor suppression must be weighed against the risks of HIV seroconversion or transient elevation of inhibitor levels, as well as against the cost of the factor concentrate used.