The efficacy of an Indian preparation of immune serum globulins (ISG) was evaluated among pregnant women during an epidemic of hepatitis E in Karad, Western India from January to March 1993. Ten of 55 women receiving ISG developed immunoglobulin M (IgM) antibodies to hepatitis E virus (anti-HEV) during the 1 month of follow-up compared with 18 out of 53 control subjects. Although the total number of recent HEV infections was significantly less in the ISG-treated group, no significant difference could be shown in the proportion of clinical hepatitis E cases because of the very small numbers of patients who developed clinical disease. The observed marginal beneficial effect of ISG might be the result of a low immunoglobulin G (IgG) anti-HEV IgG titre (1:500) of the ISG preparation used. Preparation and testing of high-titred ISG should be a high priority for protecting pregnant women during epidemics of hepatitis E.