We have determined the chromosomal location of the genes for the human keratin intermediate filament proteins K1 (type II; 67 kDa) and K10 (type I; 57 kDa) by the use of specific cDNA clones in conjunction with somatic cell hybrid analysis and in situ hybridization. The K1 keratin gene maps to chromosome region 12q11----q13; the K10 keratin gene maps to chromosome region 17q12----q21. Each gene has been mapped relative to other genes known to be localized on chromosomes 12 and 17, respectively. In somatic cell hybrid analysis, the K1 gene segregates concordantly with the Hox-3 homeo box gene cluster at chromosome region 12p12----q13. The K10 gene localizes to a region proximal to a breakpoint at 17q21 which is involved in a t(17;21)(q21;q22) translocation associated with an acute leukemia. K10 appears to be distal (telomeric) to the gene loci for G-CSF, erb-A, and Her-2, which map to chromosome region 17q12----q21. The NGFR gene and Hox-2 homeo box locus are localized distal to the 17q21 break point and thus distal to the K10 gene. These data demonstrate that keratin genes K1 and K10, which are coexpressed in terminally differentiated epidermis, are not linked in the human genome, implying the existence of trans-acting factors involved in the regulation of expression of these genes.