Kawasaki disease (KD) is the leading cause of acquired heart disease in children in the United States. The etiology is unknown. Data regarding the presence of T cell activation and its potential role in the pathogenesis of the disease have been conflicting. Expansion of T cells bearing V beta 2 and V beta 8 has recently been reported in the acute phase of KD, which suggests that a superantigen may mediate the disease process. To further assess the potential role of T cells in KD, T cell phenotypes were evaluated by using flow cytometry in a large series of patients, acutely and during convalescence. Included in this analysis were assessments of changes in the percentage of T cells bearing TCR V beta 2, V beta 5.1, V beta 6.7, V beta 8, V beta 12.1, and V beta 19 over time; the percentage of each V beta family bearing the activation markers HLA-DR and IL-2R; and the percentage of each V beta family bearing the memory marker, CD45RO. No expansion of any V beta family was present acutely, nor were increases in HLA-DR and IL-2R observed. However, a significant increase was observed during convalescence in the percentage of cells bearing CD45RO in the CD8+, but not the CD4+, population. CD45RO expression was also increased on V beta 2, V beta 8, and V beta 19 CD8+ T cells in a subset of patients. These data suggest that one or more conventional Ags drive the T cell immune response in KD, and argue against a role for superantigens in the disease process.