Recent reports by several laboratories indicate that not all nonessential target loci are equally capable of detecting chromosomal mutations. The present study was undertaken to compare the ability of the tk locus in mouse lymphoma cells and the hgprt locus in CHO cells to quantitate chromosomal mutations. Seven known mutagens for the tk locus were selected for evaluation. From these investigations, it appears that only those compounds that induce significant numbers of large-colony tk mutants also induce significant numbers of hgprt mutants. Aberration analysis revealed that both the mouse lymphoma and CHO cells responded to the clastogenicity of the compounds and that neither cell line was clearly more sensitive to the clastogens tested. The present study adds to the increasing number of studies that support the view that the hemizygous nature of the hgprt locus permits the recovery of mutations primarily affecting the function of a single gene; whereas the heterozygous nature of the tk locus permits the recovery of both single gene and chromosomal mutations.