Immunodeficient patients who were presumed to be susceptible received zoster immune globulin prophylaxis after exposure to varicella. The highest clinical attack rate (35.9%) was seen in household contacts; the lowest attack rate (0%) was observed in children exposed at school. Among household contacts, 48 of 100 patients who received high titer ZIG (reciprocal complement fixation titer greater than or equal to 2,560) developed fourfold rises in serum CF antibody between pre- and 48-hour post-treatment specimens, compared to only one of 34 patients treated with lower titer ZIG lots (P less than 0.001). Patients who developed fourfold antibody rises were significantly less likely to contract clinical varicella (P less than 0.01). Patients who received high titer ZIG also had significantly lower risks of death (P = 0.025) and complications (P = 0.006). Among ZIG-treated patients who contracted clinical varicella, 80% developed mild disease (less than 100 pox), and the median incubation period was prolonged. Immunodeficient children exposed to varicella benefit from ZIG prophylaxis and higher titer ZIG is of greatest benefit.