- A trial of pre-exposure immune serum globulin (ISG) vs. the prevailing policy of post-exposure ISG for the prevention of viral hepatitis was undertaken among 23,447 male and female military recruits in Israel, an endemic area for hepatitis A virus infection. We are reporting on the three-year follow-up of the incidence of non-B hepatitis among 12,835 male recruits, half of whom had been allocated to receive ISG on their first day of service, while the other half served as a non-vaccinated (“regular care”) control group. Over the three-year period the overall cumulative incidence in the intervention group was half that of the control group (3.6 per 1000 vs. 7.2 per 1000; p=0.0037). Protection was virtually absolute for up to nine months' follow-up. ISG may have provided prolonged partial protection well in excess of six to nine months. Between 10 to 18 months, half as many cases occurred in the intervention group as in the controls. By 18 months the difference in incidence between the study groups had reached a plateau and was highly significant (p=0.002). Between 19 and 36 months the case increment in the two groups was similar. The benefit of receiving pre-exposure ISG remained evident three years after inception of the trial in this indigenous military population living in an endemic area.