We examined clinical and immunologic factors that might affect the development of zoster in HIV-infected children. A previous collaborative study(JID 176: 1496, 1997) suggested that HIV-infected children with low CD4 levels at onset of varicella are at extremely high risk to develop zoster compared to HIV-infected children with relatively normal CD4 lymphocyte levels. We sought to determine whether HIV-infected children being followed at Babies and Children's Hospital in New York City, had a similar incidence of zoster. We therefore conducted a retrospective analysis of 33 HIV- infected children with a past history of varicella only from our clinic. Five of these children had been included in the retrospective study; 28 were new cases. The analysis included data that had been collected prospectively as part of clinical trials in which these children were enrolled. The mean age at onset of varicella was 5 years. CD4 levels ranged from 2-39% at onset of varicella. Specific antiviral therapy was given to over half the children. Varicella tended to be more severe than that seen in healthy children, but hospitalization was rare and no fatalities occurred. In two patients, there was no change in HIV viral load two months following varicella. The main threat from VZV in HIV-infected children appeared to be development of zoster. Twelve of the 33 infected children developed subsequent zoster infections. Zoster was not severe but 3/12 (25%) had recurrent episodes. The mean age at onset of zoster was 9.5 years. We found that as in the earlier collaborative study, CD4 lymphocyte levels at the onset of varicella were significantly lower in children who went on to develop zoster compared to those who did not. The incidence of zoster in children with CD4 levels that were less than 25% at varicella onset was 6/11(54%) over a period of several years. In 13 children who had varicella when their CD4 levels were equal to or greater than 25%, there were no cases of zoster during a similar interval (p =.001). These data suggest that immunization of HIV-infected children who have relatively normal CD4 levels and who have not previously had varicella may contribute significantly to their quality of life. In order to be most effective, immunization should be carried out ideally as soon as possible after 1 year of age.