The Terena Amerindians are located in the midwestern region of Brazil. We have previously reported a restricted polymorphism for HLA class I and class II in 99 unrelated Terena using PCR-SSO and more recently for MICA. There are single nucleotide polymorphisms (SNPs) that determine high or low production of certain cytokines. We have now studied the frequencies of mutant allele (A) at position −308 in the promoter of the gene tumor necrosis factor (TNF)-α (pro-inflammatory cytokine) and the alleles A and T, at position −1082 and −819, respectively, in the promoter of the interleukin (IL)-10 gene, in 51 of these subjects from the Terena tribe using PCR SSP and in 195 normal unrelated healthy Brazilians using PCR-RLFP. All 51 Terena Indians tested (100%) had the G/G genotype at position TNF-α −308, with no mutation found thus far. In contrast, among the Brazilian general population, the allelic frequency of A was 18.9%. When anti-inflammatory cytokine IL-10 was studied at two different positions, −1082 and −819, a high mutation rate was found when Terena were compared with the general Brazilian population (P < .05). The genetic cytokine profile may be required to balance the restricted HLA repertoire for peptide presentation in this native population.