Serum antibody levels against varicella-zoster virus (VZV) were examined by immune adherence hemagglutination assay (IAHA), indirect fluorescent antibody (IFA) assay, and complement fixation techniques in 67 immunocompromised patients with localized and disseminated herpes zoster. In the serum obtained initially, undetectable IAHA titers were found in 56.5% of the patients with disseminated zoster compared with 18.2% of those with localized zoster. When serum obtained within the first seven days of illness was analyzed, undetectable IAHA titers and IFA titers of < 32 were noted in 77.8% of those with disseminated zoster but in only 18.5% of those with localized disease. Peak serum antibody titers in patients with disseminated zoster were eventually equal to or greater than those in localized zoster. The patient groups were comparable in age, underlying disease, and therapy, although Hodgkin's disease was more frequent in patients with disseminated zoster. Thus, the absent IAHA or low IFA levels of circulating antibody early in illness were highly significant risk factors in dissemination of virus in herpes zoster. © 1979, American Medical Association. All rights reserved.