The human tumor necrosis factor locus (TNF locus) is located within the major histocompatibility complex between the class III genes and HLA-B. We recently characterized and studied two closely linked highly informative dinucleotide repeats (AC/GT)(n) (designated TNFa) and (TC/GA)(k) (designated TNFb) in the upstream region of the human TNF-lβ (lymphotoxin) gene. We also characterized two linked (TC/GA) and (TC/GA)-like repeats located downstream of the TNF-α gene, designated TNFe and TNFd, respectively. Here, we combine these Pour markers together with a biallelic TC/GA repeat in the first intron of the TNF-β gene (TNFc) and a biallelic NcoI RFLP (TNFn) to type 105 cell lines from the American Society of Histocompatibility and Immunogenetics Workshop and the Center for Human Polymorphism Studies reference panels of HLA typing cell lines. These 6 polymorphic markers define 35 distinct TNF haplotypes and together with the reference panel can be used for disease association and population genetics studies. © 1993 Academic Press, Inc.