Secretory ameloblasts in the continuously growing incisors of the rat were used to study the sequential changes in a mature cell type degenerating after administration of vinblastine at a dosage of 2 mg per kg body weight. In less than half an hour nearly all microtubules vanished. This was succeeded by progressive displacement of the nuclei and disorganization of the cytoplasmic structure. After 1 to 3 hours attached and free polyribosomes were converted into monoribosomes. All these cytoplasmic changes were seen in viable as well as in necrotic cell. Between 5 and 61/2 hours after application of the drug degeneration of nuclei began; these changes from the outset indicated that a particular ameloblast had been drawn into a sequence of events which would ultimately lead to its death. The progressive alterations of the nucleus and cytoplasm of the degenerating cells and the concurrent fragmentation and elimination of the fragments are described.