HIV phenotype [syncytia inducing (SI) or non-syncytia inducing (NSI)] is an important characteristic of the virus which reflects its tropism and potential virulence. To better understand the relationship of phenotype to clinical status and prognosis, phenotypic information was obtained on 75 children with HIV infection who were participating in a study of influenza vaccine and its effect on RNA copy number. Phenotypic determinations were made using the MT-2 cell line on isolates obtained in the Fall, 1994, and follow-up clinical information was obtained for the next two years. 56 children were NSI, 19 SI. Significant differences between the NSI and SI populations were seen in:(medians, NSI vs. SI) CD4 Count (770 vs. 100, p=0.0001 (2-tailed Wilcoxon)), CD4 Percentage (29 vs. 5, p=0.0001), and Age (4.90 vs. 7.16 years, p=0.04). The difference in log 10 RNA copy number was almost significant (4.57 vs. 4.97, p=0.07). Gender and CDC Clinical Category were similar in the two(NSI/SI) groups. SI phenotype was associated with adverse outcomes. Using Kaplan-Meyer Survival Analysis of time to first CDC Category C Diagnosis or death, 10/56 NSI patients reached an endpoint, vs. 12/19 SI patients (Log Rank p=0.0001). Using Multivariate Cox Proportional Hazards Models for time to endpoint which included phenotype (p=0.004), CDC Clinical Category (p=0.009), Log 10 RNA copy number (p=0.007), age (p=0.14) and CDC Immune Category(p=0.07), the first three variables significantly contributed. Much of the effect attributable to phenotype may be related to the low CD4 counts seen in children with SI virus. Conclusion: SI phenotype is associated with more severe HIV disease and depletion of CD4 cell populations. RNA copy number was similar in the two phenotype categories.