The gastrointestinal form of Chagas disease is characterized by lumenal enlargement and wall thickening of the esophagus and/or colon. Very little is known about the involvement of the immune system in the development of the gastrointestinal form of the disease. In this paper we describe our initial observations on the phenotypic analysis of peripheral blood mononuclear cells from patients with the gastrointestinal form of Chagas disease. A significant decrease in the absolute number of CD3(+) T cells as well as in CD19(+) B lymphocytes was observed. However, the most striking observation was an inversion of the CD4/CD8 ratio, contrasting with results from cardiac chagasic patients in whom the ratio is normal. A decrease of the percentage of CD4(+)CD28(+) cells and an increase in the expression of HLA-DR both on CD4(+) and on CD8(+) cells suggest that although these T cells express activation markers their function may be altered by the lack of CD28 expression.