We investigated five single-nucleotide polymorphism (SNP) sites of tumor necrosis factor-alpha (TNF-alpha) promoter, the distribution of five-locus TNF-alpha haplotypes, and extended human leukocyte antigen (HLA)/TNF-alpha haplotypes in 200 parents from 100 unrelated Korean families. TNF-alpha SNPs were typed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and PCR restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of -1031C, -863A, -857T, -308A, and -238A alleles were 0.185, 0.145, 0.140, 0.060, and 0.040, respectively. The allele frequencies in Koreans were similar to those of Japanese. A total of five TNF-alpha haplotypes (-1031/-863/-857/-308/-238) were detected in 196 parents: TCCGG (frequency 0.617), CACGG (0.143), TCTGG (0.143), TCCAG (0.061), and CCCGA (0.036). Five most common extended HLA/TNF-alpha haplotypes (frequencies >0.020) accounted for 16% (63/392) of the total haplotypes. A total of 223 HLA haplotypes and 239 HLA/TNF-alpha haplotypes were detected, indicating that most HLA haplotypes are exclusively associated with particular TNF-alpha haplotypes.