Two genetic epidemiological studies were carried out in the Ivory Coast and Democratic Republic of Congo to assess the role of human genetic diversity in susceptibility to human African trypanosomiasis (HAT). Findings showed that four single DNA polymorphisms located on genes coding for cytokines were correlated with a variable risk for development of the disease. Whereas presence of the rare A and T alleles for IL10 592 C/A and IL6 4339 C/T polymorphisms appeared to protect against HAT, presence of the T allele and AA genotype for IL1 5417 C/T and TNFalpha-308 G/A polymorphisms were correlated with an increase in HAT risk. These results will improve understanding of the host-parasite interaction and, ultimately, assist the development of new therapeutic and prophylactic tools.