The available evidence suggests that plasma leakage in dengue hemorrhagic fever is caused by the action of circulating mediators on the vascular endothelium, and that the host immune response is a critical determinant of this response. We have been exploring the role of dengue virus-specific T lymphocytes in the immunopathogenesis of plasma leakage. Memory dengue virus-specific T cells induced during a primary dengue virus infection are reactivated by the heterologous viral serotype during a secondary infection to expand to high levels and produce a skewed cytokine profile. Investigations are underway to identify the immunologic profiles associated with increased or decreased risk for severe disease.