The gene encoding histidyl-tRNA synthetase was localized to human chromosome 5 using human-Chinese hamster ovary cell hybrids. Seven of the functionally related genes encoding the 20 different aminoacyl-tRNA synthetases have not been mapped in humans and four are located on a single chromosome, number 5, which represents less than 7% of the total genome. Thus, there appears to be significant clustering of this group of genes which may reflect their evolutionary relatedness or common factors involved in regulating their expression.