Removal of the olfactory organ in adult zebrafish results in a significant decrease in volume of the ipsilateral olfactory bulb. The current study investigated the potential role of apoptosis in this phenomenon. It was hypothesized that cells in the adult olfactory bulb normally undergo minimal apoptosis and that apoptosis increases upon removal of sensory stimulation. By using both the terminal transferase-mediated deoxyuridine nick-end labeling method and bis-benzimide labeling, the current study showed that, in the normal adult olfactory bulb, cells exhibiting apoptotic profiles were scarce and were localized to the outer layers of the bulb. However, in deafferented animals, there was a significant increase in the number of apoptotic cells. The apoptotic response occurred in two phases and was confined to the rostral half of the bulb. The first phase of cell death peaked at 1 hour postsurgery. These apoptotic profiles appeared to be primarily nonneuronal in nature, in that they exhibited no immunohistochemical labeling to the neuron-specific protein Hu. The second phase of cell death peaked at 24 hours and declined to normal levels by 1 week. At the 24 hour time point, only a fraction of the apoptotic cells was neuronal in nature. Thus, apoptosis of nonneuronal and neuronal elements accounts for at least part of the deafferentation-induced volume decrease in the zebrafish olfactory bulb. This model of anterograde transneuronal degeneration will be useful in elucidating the afferent signals involved in survival and maintenance of mature brain neurons.