A prospective study was carried out in 46 patients suffering from severe malaria. The control group included 220 persons of which the HLA-DR distribution was known. The HLA-DRB1 alleles were typed by PCR-SSP (Sequence Specific Primers). The most frequent HLA-DR alleles found in patients group were: DR52 (82.8%), DR13 (57.1%), DR10 (28.6%), DR53 (25.7%), DR3 (20%), DR18 (20%). A significant difference was observed between patients with severe malaria and control group for the following alleles: DR3, DR10, DR13 (p < 0.001; Chi square with Yates' correction) and their relative risk were respectively 14.67; 6.29; 2.84. HLA-DR3 was considered as the major marker associated to severe malaria.