Chagas disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis, and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system components leads to megacolon development. Besides neurons, the enteric nervous system is constituted by enteric glial cells, representing an extensive but relatively poorly described population within the gastrointestinal tract. Several lines of evidence suggest that enteric glial cells represent an equivalent of central nervous system astrocytes. Previous data suggest that enteric glia and neurons are active in the enteric nervous system during intestinal inflammatory and immune responses. To evaluate whether these cells act as antigen-presenting cells, we investigated the expression of molecules responsible for activation of T cells, such as HLA-DR complex class II and costimulatory molecules (CD80 and CD86), by neurons and enteric glial cells. Our results indicate that only enteric glial cells of chagasic patients with megacolon express HLA-DR complex class II and costimulatory molecules, and hence they present the attributes necessary to act as antigen-presenting cells.