Serial chromosome analyses with a mean of 3.7 samplings during a mean interval of 4.2 years (range, 1.5 to 8.6 years) were performed on B-cell mitogen-activated chronic B-lymphocytic leukemia (CLL) cells from 41 patients. Twenty-four of these patients (59%) had progressive disease. Clonal chromosomal aberrations were found in 28 patients; 12 had an extra chromosome 12. Thirty patients (73%), 17 with and 13 without clonal aberrations, retained their karyotype throughout the study, although six lost minor subclones. In five patients (12%), a clonal aberration was found only once. Six patients (15%) showed changes of the karyotype. One treated patient with multiple aberrations acquired another monosomy. Another patient with multiple aberrations and prolymphocytic transformation gained a marker chromosome. One treated patient with an initially normal karyotype acquired two independent clonal aberrations. Three patients lost one subclone but retained another clone that increased in frequency. In two cases, clonal changes were associated with clinical changes. The chromosomal aberrations are mostly established already at diagnosis and mark the disease of the CLL patient. Cytogenetic analysis at any time is representative and useful in the prognosis prediction.