In the last 30 years patients with antibody deficiency have benefited remarkably from regular replacement therapy with intramuscular immune serum globulin. In a proportion of patients this approach has not been successful in preventing sinopulmonary infections and progressive deterioration. The introduction of preparations of immune serum globulin suitable for intravenous administration provided the potential for examining the effects of achieving higher serum IgG levels. We have therefore evaluated and compared high vs low dose therapy in patients with hypogammaglobulinemia and sinopulmonary disease. To achieve minimum trough serum IgG levels of 500 mg/dl, we administered 0.6 g/kg every 4 weeks. High dose therapy proved efficacious in reducing symptoms, decreasing the frequency of major and minor infections and significantly improving pulmonary function. The improvement appeared to correlate with a marked reduction in the isolation of Mycoplasma, particularly Urea-plasma urealyticum, an important cause of infection in patients with hypogammaglobulinemia. High dose therapy with immune serum globulin suitable for intravenous administration appears to be the treatment of choice in patients with sinopulmonary disease.