T-Lymphocyte clones from healthy males and females and from melphalan-treated ovarian carcinoma patients were studied with regard to sporadic chromosomal aberrations and clonal karyotype: 85% of the clones showed a normal, diploid karyotype, and sporadic aberrations were found to occur at about the same low frequency as in short-term lymphocyte cultures. An abnormal karyotype was found in 11 of the 72 clones studied. Loss of an X chromosome, which was the most frequent abnormality in female clones, was verified by densitometry of Southern blots of clonal DNA hybridized with a probe for the X-linked hprt locus. Abnormal karyotype due to chromosomal rearrangement was found in nine clones, and, in five of these, chromosome 12 was involved in the aberration. About 33% of the clones from melphalan-treated patients had an abnormal karyotype, in comparison with about 10% of clones from healthy control subjects. This difference indicated that melphalan treatment may induce stable chromosomal rearrangements that are compatible with cellular proliferation and clonal expansion.