The process of human chromosome segregation in human myeloma x mouse myeloma cell hybrids was investigated. The human myeloma cells were derived from two different patients. Fifty-eight independent hybrid lines were obtained. A representative number of cells from each line were karyotyped and isozyme markers for a number of the chromosomes retained were analyzed. Statistical analyses were performed on 113 cells from five different cell lines showing the largest complement of human chromosomes. A log-linear models approach to the statistical analysis was used to predict the expected chromosome segregation under a variety of assumptions concerning the dependency relationship between the pattern of loss and the specific chromosomes both within and between cell lines. Human chromosome segregation occurring after the hybrids were grown continuously in suspension for several months was also studied. Results indicated a statistically significant dependency among patterns of loss of specific chromosomes, with certain chromosomes preferentially retained and others lost more often than expected under the assumption of randomness of segregation.