The effect of prolonged, high-dose corticosteroid therapy on total IgG synthesis rates by human bone marrow and splenic leukocytes was studied in patients with immune thrombocytopenia. Marrow IgG production rates begin to decrease 3 weeks after beginning therapy and reach levels approximately one-fourth of pre-treatment rates after 6 weeks. No effect of corticosteroids on splenic IgG production rates could be shown. Marrow IgG synthesis rates in these patients were on the average from 3 to 10 times greater than corresponding splenic production rates and, in addition, appeared to correlate with serum IgG levels. These data suggest that the marrow is an important contributor to the total body IgG pool; and since corticosteroids appear to suppress marrow IgG production, this may be one reason for their therapeutic usefulness in antibody-mediated diseases.