Purpose: To examine the prevalence of anergy in HIV-infected adolescents and factors associated with its occurrence. Methods: Anergy was defined as less than 2mm induration to each of three intradermally applied antigens (Candida albicans, tetanus toxoid, and mumps) between 24 and 96 hours in a population of HIV-infected adolescents aged 12-18 at entry in a national multicenter study of HIV disease progression. CD4+ T-cell counts and plasma HIV-1 RNA were measured in quality controlled laboratories. Factors associated with the probability of anergy were examined with contingency table comparisons, tree-structured classification, and logistic regression analyses. Results: Overall prevalence of anergy in this clinic-based population of 167 was 11% [7% in males and 12% in females (p = 0.57)]. The sole significant predictor of anergy was decreased CD4+ T-cell count (p = 0.005). Conclusion: The prevalence of anergy is low in this HIV-infected population compared to older infected cohorts. The occurrence of differential rates of anergy in particular age and sex groupings that may be related to intrinsic immunologic differences requires further study. Copyright (C) 2000 Society for Adolescent Medicine.