Allele frequencies (AFs) and haplotypic associations of human leukocyte antigen (HLA) class I and II were investigated in 400 unrelated, healthy, ethnic Northeast Thais. HLA-A, -B, -Cw, -DRB1 and -DQB1 were typed by polymerase chain reaction-sequence specific primer, -sequence specific oligonucleotide probe and -single-strand conformation polymorphism methods. In this population, 17 HLA-A, 26 HLA-B, 15 HLA-Cw, 26 HLA-DRB1 and 13 HLA-DQB1 alleles (or groups of alleles) were found. AFs > 10% included A*11 (23.3%), 24 (18.8%), 0207 (14.4%), 33 (11.5%), 0203 (10.6%); B*4601 (13.9%); Cw*07(01-03) (18.5%), 01 (15.9%), 04 (12.0%), 0304 (10.6%); DRB1*1502 (18.5%), 1202 (13.4%); DQB1*0502 (20.3%), 0501 (16.3%), 0301 (14.1%) and 02 (10.9%). The most common of 2-locus haplotypes included A*0207-B*4601 (9.3%), B*4601-Cw*01 (13.5%), B*5801-DRB1*0301 (5.8%) and DRB1*1502-DQB1*0501 (14.1%). Of the 49 five-locus HLA haplotypes identified, 24 were confirmed in 31 family studies: the most common being; A*33-Cw*0302-B*5801-DRB1*0301-DQB1*02 (4.6%), A*0207-Cw*01-B*4601-DRB1*09-DQB1*0303 (3.4%) and A*33-Cw*07(01-03)-B*44-DRB1*07-DQB1*02 (2.6%). Apparently, the HLA-B*46-carrying haplotype is fragmented in ethnic Northeast Thais, including seven haplotypes with different HLA-A and HLA-DR/DQ combinations. One of these haplotypes (A*11-Cw*01-B*4601-DRB1*1202-DQB1*0502) has not been reported in other Asians. The results indicated that there were marked differences in the distribution of HLA alleles and haplotypes between ethnic Northeast Thais and other ethnic groups in Southeast and East Asia. These results also dictate that future studies of HLA alleles and diseases need precise identification of ethnically and geographically matched controls. The HLA allele and haplotype analyses in this large sample provide baseline information on ethnic Northeast Thais for anthropological studies and for determining HLA allele/haplotype frequencies when searching for HLA-compatible donors for unrelated bone marrow transplantation.