The association between the presence of CCR5 Delta32 heterozygosity and incidence of clinical herpes zoster was studied among 296 homosexual men from the Amsterdam cohort study (ACS) infected with human immunodeficiency virus type I (HIV-1) with an estimated date of seroconversion. Of them 63 were CCR5 Delta32 heterozygotes and 233 CCR5 wild-type. The incidence rate of a first episode of herpes zoster was 4.2% and 5.3% per person-year, respectively. A higher occurrence of herpes zoster was strongly related to a lower CD4 + cell count. After adjustment for age, presence of CCR2b 64I heterozygosity, HIV RNA load, time since seroconversion, and CD4 + cell count, the rate ratio for herpes zoster of CCR5 Delta32 was 0.9 (95%CI 0.5-1.6). In conclusion, in HIV-1-infected homosexual men, a CCR5 Delta32 heterozygous genotype has no protective effect on the incidence of herpes zoster.