Acute rheumatic fever (ARF) and its chronic valvular sequelae are the delayed consequence of a pharyngeal infection with group A Streptococcus (GAS). Several GAS proteins have been shown to be superantigens, raising the possibility that the expansion or deletion of T cells expressing specific Vbeta regions might play a role in the pathogenesis of ARF or chronic rheumatic heart disease (RHD). We therefore analyzed by four-color flow cytometry, the Vbeta repertoire on CD3, CD4 and CD8 T cells from four ARF patients, 10 RHD patients and also nine healthy controls. A selective depletion of Vbeta2+ T cells was found only in the CD8 subset of chronic RHD patients. This is of interest since a number of GAS superantigens exert their effects on Vbeta2+ cells and because only CD8+ T cells from ARF and RHD patients undergo anergy in response to GAS superantigens. Our results suggests that an ongoing immune process is present in RHD patients and that CD8+ T cells may have an important immunoregulatory role in the pathogenesis of the disease.