Sequencing of hprt cDNA revealed that three spontaneous mutants in V79 Chinese hamster cells exhibit tandem duplications of exon(s), i.e., either exons 2 and 3 or exon 7. Sequences of different sizes (4.5-8 Kb) were found to be duplicated and inserted in tandem into the hprt gene. These mutants demonstrated spontaneous reversion frequencies which were about 40-fold higher than those observed with other types of spontaneous mutants, but on the same order of magnitude as spontaneous reversions in Sp5, a mutant with a duplication insertion involving exon 2 in this gene. These data suggest that all of the duplications found have the same genetic instability, regardless of the type, size or position of the duplicated fragment. The coding sequence of the hprt cDNA and the restriction pattern of the revertants were virtually identical to the wild-type, indicating restoration of a functional hprt gene by precise deletion of the duplicated fragment.