A 44-year-old woman with refractory immune thrombocytopenia purpura was treated with the murine monoclonal antibody 197 in a phase I trial. In vitro studies have demonstrated that the monoclonal antibody 197 (subclass IgG2a) binds to two distinct epitopes of FcγRI, with the constant domain binding to the Fc-binding portion of the FcγRI and the variable domain binding to a different epitope, resulting in crosslinking and modulation of this receptor. The monoclonal antibody 197 was administered on days 1, 3 and 5 at doses of 0.25 mg/kg, 0.35 mg/kg and 0.45 mg/kg, respectively. The infusions were well tolerated with transient facial flushing, and wheal-and-flare rash during the first infusion, which resolved with a slower infusion rate and the administration of diphenhydramine and acetaminophen. Although a marked clinical improvement did occur with resolution of oral ecchymoses and epistaxis after the first mAb infusion, the initial platelet count of 6×109 l did not change appreciably over the 5 d course of monoclonal antibody treatment. Binding of fluorescein-labelled monoclonal antibody 197 to peripheral monocytes showed a rapid and persistently decreased mean fluorescence intensity, indicating binding of administered 197 to the monocytes in vivo. Indirect staining for FcγRI using fluorescein-labelled goat anti-mouse immunoglobulin was also decreased, suggesting modulation of the receptor. The patient experienced monocytopenia which persisted throughout the 5 d of monoclonal antibody 197 therapy, but reversed following institution of intravenous IgG. These data indicate that intravenous monoclonal antibody 197 induces specific down-modulation of FcγRI expression on monocytes.