The DRB, DQA, and DQB subregions of the major histocompatibility complex (MHC) were investigated by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization (PCR/SSO) in 103 multiple sclerosis (MS) patients and 101 healthy controls from Turkey. Significant differences were detected between MS and control populations in the frequencies of DRB1*1501 [29 vs. 14, p = 0.02, odds ratio (OR) = 2.4], DRB1*04 (35 vs. 18, p = 0.01, OR = 2.3), DQB1*0302 (30 vs. 15, p = 0.02, OR = 2.3), DQB1*0602 (27 vs. 10, p = 0.005, OR = 3.2), DQB1*0501 (10 vs. 24, p = 0.01, OR = 0.3), DQA1*0101 (16 vs. 31, p = 0.02, OR = 0.4), and DQA1*0103 (7 vs. 19, p = 0.02, OR = 0.3). These results confirm the proposed positive association of the Dw2 (DRB1*1501 DQA1*0102 DQB1*0602) haplotype with MS in Caucasians in our Turkish population (25 vs. 8, p = 0.003, OR = 3.7). Furthermore, the "putative" haplotype supposed to be more frequent in the MS population of Mediterranean countries, namely DRB1*04 DQA1*03 DQB1*0302, is also associated with MS in Turkey (29 vs. 12, p = 0.006, OR = 2.9). The presence of two different haplotypic associations in MS emphasizes the complexity of the genetic susceptibility to MS in different populations.