The aim of this study was to investigate whether the promoter's polymorphisms at the TNF alpha (TNF-alpha) gene were associated with the genetic susceptibility to Chagas' disease. We analyzed the TNF-alpha (positions -308, and -238) polymorphisms in a sample of 54 serologically positive chagasic individuals and in 169 healthy controls. The patients were divided according to clinical characteristics as asymptomatics (n = 27), and chronic chagasic cardiopathy (CCC) patients (n = 27). The whole group of patients showed increased frequencies of -308 T2 (A) allele when compared to healthy controls (pC = 0.008, OR = 3.03). When the analysis was carried out separately in asymptomatic and CCC patients, increased frequencies of T2 (A) allele and T1T2 (AG) genotype in the group of patients with CCC were found when compared to asymptomatic individuals (pC = 0.0002 and pC = 0.003, respectively) and healthy controls (pC = 4 x 10(-7), OR = 7.02, and pC = 0.0006, OR = 5.29, respectively). The present study demonstrates that Chagas' disease is associated with TNF-alpha polymorphisms in the Mexican population. The TNF-308 T2 allele could be directly involved in the genetic susceptibility to the chronic phase of the disease.