The frequency of sperm aneuploidy was investigated by fluorescence in situ hybridization (FISH) in a Hodgkin's disease patient shortly after he had received chemotherapy and radiotherapy. Sperm karyotyping of the same patient had previously shown multiple structural abnormalities in most spermatozoa immediately after radiotherapy (day 0), whereas most spermatozoa collected 5 wk later (day 38) exhibited normal metaphase divisions (Rousseaux et al., 1993). Variations in the frequency of aneuploidy could not be detected by sperm karyotyping. Multicolor FISH on interphase spermatozoa revealed an increase in the rate of disomy for chromosomes 1, 6, 11, X, and Y at day 0 as well as at day 38. The high frequency of 24,XY (nondisjunction at meiosis I) and 24,XX (nondisjunction at meiosis II) spermatozoa (8.46% and 1.64% at day 0, respectively) from the Hodgkin's disease patient suggests that both meiosis I and II are affected and that the X chromosome is frequently involved in such malsegregation events. The rate of 46,XY diploidy was also increased in the patient's sperm, up to 0.62% at day 0. While radiotherapy probably affected the postmeiotic cells (spermatids), the patient's cancer and/or chemotherapy are the two major factors that could have affected the dividing spermatogonia and/or spermatocytes, resulting in high aneuploidy rates.