To determine whether intravenous immunoglobulin (IVIg) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection, chronic graft-vs.-host disease (GVHD), and obliterative bronchiolitis after marrow transplantation, patients were assigned randomly to receive either IVIg (500 mg/kg/month) or no IVIg prophylaxis. Participants were registered before transplantation, and 250 patients (123 IVIg and 127 control) were evaluable for events after day 100. The two groups were balanced for age, marrow source, cytomegalovirus (CMV) seropositivity, pretransplantation conditioning, and prophylaxis for infection and GVHD. Between days 100 and 365 posttransplantation, the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls (p = not significant). During the same period, the incidence of localized infection was marginally higher in control patients than in IVIg recipients (0.44 vs. 0.24, respectively; relative risk [RR] 1.46, p < 0.07). Administration of IVIg prophylaxis had no effect on survival, the incidence of obliterative bronchiolitis, severity of airflow obstruction, or the incidence or mortality of chronic GVHD. After discontinuing IVIg prophylaxis at day 360, subsequent recovery of endogeneous humoral immunity was impaired (serum IgG1 and IgA levels were significantly lower than controls at day 730), and total infections were less common in the second year in control patients than in former IVIg recipients (0.12 vs 0.19, respectively; RR 0.61, p = 0.03). We conclude that in the absence of hypogammaglobulinemia, monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation.