Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin's disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin's disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin's lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25 --> q27, that have also been reported may show some specificity for Hodgkin's disease.