Hall, W. T., D. L. Madden (National Institutes of Neurological and Communicative Diseases and Stroke, Bethesda, MD 20014), F. K. Mundon, D. E. L. Brandt and N. A. Clarke. Protective effect of immune serum globulin (ISG) against hepatitis A infection in a natural epidemic. Am J Epidemiol 106:72–75, 1977. Serologic evidence now confirms epidemiologic evidence that human immune serum globulin (ISG) protects susceptible patients from hepatitis A provided it is administered prior to exposure to the virus. In two wards of young patients housed at the Lynchburg (Virginia) Training School and Hospital for the mentally retarded, 44 out of 60 patients had no detectable antibody to hepatitis A prior to an epidemic which took place there in 1970; 12 of 19 non-Immunized susceptible patients contracted the disease, while only four of 25 patlents receiving ISG developed hepatitls. These four were probably infected with the virus prior to ISG administration. Of the 16 patients with preexisting antibody, none showed any signs or symptoms of hepatitis.