Infection has been recognized as an important cause of morbidity and mortality in children with nephrotic syndrome. However, the incidence and severity of infection and the mechanisms responsible for the increased susceptibility to infection are still unclear in adults. We studied 86 consecutive adult patients with nephrotic syndrome but no diabetic nephropathy. Risk factors for infection were evaluated by logistic regression analysis. Infections were found in 16 patients (19%), of whom six died of infection and two developed end-stage renal failure associated with infection. The relative risk for bacterial infection among patients with serum immunoglobulin G (IgG) levels below 600 mg/dL was 6.74 compared with that for patients with serum IgG levels over 600 mg/dL (95% confidence interval, 1.22 to 36.32; P = 0.029). In patients with serum creatinine levels over 2.0 mg/dL, the relative risk of bacterial infection was 5.31 compared with patients with serum creatinine levels below 2.0 mg/dL (95% confidence interval, 1.08 to 26.09; P = 0.040). Intravenous immunoglobulin (10 to 15 g) was administered prospectively every 4 weeks to 18 patients with serum IgG levels below 600 mg/dL until serum IgG levels increased to over 600 mg/dL. Administration of immunoglobulin resulted in a decreased rate of bacterial infections to a level equal to that in patients with endogenous levels over 600 mg/dL. These data indicate that hypogammaglobulinemia and renal insufficiency are independent risk factors for bacterial infection in adult patients with nephrotic syndrome. The effects of intravenous immunoglobulin suggest that maintenance of serum IgG levels over 600 mg/dL may reduce the risk of infection.