Herpes zoster can be a severe, and sometimes fatal, virus infection in its disseminated form in immunocompromised hosts. Previous studies have suggested that delay in appearance of antibody to varicella-zoster virus occurs as one defect in such patients. In this study, pooled gamma-globulin (normal serum globulin [NSG]) and zoster immune globulin ([ZIG] prepared from convalescent zoster patients) were compared for their ability to prevent dissemination of early localized zoster in immunocompromised hosts. Either agent was given intramuscularly in randomized double-blind fashion within nine days of onset of zoster in 97 patients. Despite greater than 100-fold differences in titer of anti-varicella-zoster virus antibody, ZIG did not appear superior to NSG in prophylaxis of dissemination or diminishing postherpetic pain in zoster in immunocompromised hosts. Zoster immune globulins should be reserved for prophylaxis and modification of varicella, where its beneficial effect has been demonstrated.