Chagasic megacolon is one of the most important forms of Chagas disease. This form is characterized by inflammation, neuronal destruction and organ dilatation. The aim of this study is to characterize the expression of substance P and its main receptor, NK1 receptor, in dilated and non-dilated samples of colon from chagasic patients with megacolon. Our results demonstrate that dilated portions of colon present high levels of substance P and low levels of NK1 receptor, whereas non-dilated portions and samples from non-infected individuals present low levels of substance P and high levels of NK1 receptor. We believe that this may indicate a neuro-immune relationship that occurs in Chagas disease.