Zoster is an important clinical problem for human immunodeficiency virus type 1 (HIV)-infected patients. Risk factors for zoster and trends in incidence in HIV-infected hemophiliacs and homosexual men (n=1218) were examined. From 1984 to 1997, 174 zoster cases were identified (average yearly incidence, 2.5%). Prior zoster episodes were associated with increased risk for a subsequent episode (relative risk [RR], 4.30; 95% confidence interval [CI], 3.11-5.95). Among hemophiliacs, children and adolescents had the highest zoster risk, and zoster risk declined with age (RR, 0.80 per decade; 95% CI, 0.68-0.93). These findings suggest that HIV-infected persons do not produce or maintain adequate booster responses after varicella zoster virus exposure. Zoster risk was relatively constant when CD4 cell counts >200 cells/mm3 but increased steeply below this level. During the 14 years of follow-up, zoster incidence declined 9% per year. This trend occurred despite decreasing CD4 cell counts and was unexplained by zidovudine or acyclovir use.