The acute effect of vinblastine sulphate at a dosage of 0.2 mg per 100 g body weight on ameloblasts in the progress of differentiation in rat incisors, and the ability of these cells to develop into secretory ameloblasts after exposure to the drug, were studied under the light microscope. In the early stages of differentiation (exclusively dividing cells) no changes were seen. In more advanced stages of differentiation the cell apices were altered and the nuclei normally placed near the cell base were located at all levels in the ameloblast layer. These changes were reversible and the cells developed into secretory ameloblasts of normal appearance and function. Ameloblasts in the most advanced stage of differentiation in which secretion had begun were severely damaged, and the mature secretory ameloblast population derived from these cells was decimated and produced enamel matrix with abnormal structure. It is concluded that differentiating ameloblasts are relatively invulnerable to vinblastine, whereas in secretory ameloblasts the organelles directly engaged in the secretory processes are particularly exposed to damage from the drug.