Thymidine autoradiography has been used at light and electron microscopic levels to elucidate intracellular events during the death in chick embryos of isthmo-optic neurons deprived of trophic maintenance from their axonal target organ, the retina. When the intense cytoplasmic vacuolization described in the accompanying paper (Hornung, Koppel, and Clarke, J. Comp. Neurol. 283:425-437, '89) was beginning, the nuclei also underwent profound changes. They became more electron dense and shrank; their membranes became more sharply defined and convoluted; they sometimes contained pyknotic balls, but apparently only in the early stages of cell death; all lost more than half of their content of DNA, some of which was transferred to the largest kind of cytoplasmic vacuole. This transfer may have involved the budding off of nuclear regions containing pyknotic balls. The cells continued to survive for a day or 2 after these severe losses of nuclear DNA, sustaining intense endocytic activity. Pronounced unscheduled DNA synthesis occurred in the nuclei, but this was insufficient to replace the lost DNA.