The occurrence of chromosomal damage produced by the pyrrolizidine alkaloid heliotrine in Drosophila has been demonstrated using the frequencies of induced dominant lethals, partial and complete sex-chromosome loss, translocations and sex-ratio shifts as measures of the resulting damage. It has been shown that the frequency of XO males induced by the alkaloid is insufficient to account for the observed deviation in the sex-ratio even on the unlikely assumption that all XO males result from X-chromosome loss. Therefore it is proposed that the remaining deviation is due to the differential production of dominant lethals in the X- and Y-bearing sperm. Assuming that all XO males result from X-chromosome loss, and dominant lethals are produced in a ratio of 1:0.85 for the X- and Y-bearing sperms respectively, then a close fit with the experimentally observed sex-ratios is obtained. Translocations are produced with a low frequency. Evidence is discussed which indicates that there is a close relationship between the frequencies of induced translocations and asymmetrical exchanges. On this basis it is concluded that the latter made an insignificant contribution to dominant lethality in Drosophila following heliotrine treatment. It is suggested that most dominant lethals arise as a result of intrachromosomal rearrangements with lethal effect, or to isochromatid aberrations. It is further proposed that the different sensitivities of the X-ray and Y-bearing sperms must be due to the different frequencies of lethals occurring in the X- and Y-chromosomes. © 1966.