Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 <P<0.01) difference was found for 5 and 12 alleles, respectively. Four alleles (A*24, A*29, B*27, B*3701) appeared to be essentially "private" Fulani alleles with respect to the other two populations but their presence was not associated with higher resistance to P. falciparum. Our data have then been compared using chord distances (CD) with those from the literature on Africans (including Gambian Fulani) and Caucasoids. The Burkina Faso and Gambian Fulani turned out to be very different (CD=2.191). Moreover, Burkina Faso Fulani were very distant from sympatric Mossi and Rimaibé (CDs=1.912 and 1.884), whereas Gambian Fulani were similar to sympatric Mandinka and Wolof (CDs=0.412 and 0.388) to an extent comparable to that found between Mossi and Rimaibé (CD=0.555). Our study does not suggest the involvement of HLA I in the higher resistance to malaria of Fulani, and confirms a low, if any, Caucasoid component in their gene pool.