Studies of the avian auditory system indicate that neurons in nucleus magnocellularis (NM) and nucleus laminaris of young animals are dramatically altered by changes in the auditory receptor. We examined the role of presynaptic activity on these transneuronal regulatory events. TTX was used to block action potentials in the auditory nerve. TTX injections into the perilymph reliably blocked all neuronal activity in the cochlear nerve and NM. Far-field recordings of sound-evoked potentials revealed that responses returned within 6-12 hr after a single TTX injection. Changes in protein synthesis by NM neurons were measured by determining the incorporation of 3H-leucine using autoradiography. NM neurons on the side of the brain ipsilateral to the TTX injection were compared to normally active cells on the other side of the same tissue section. Grain counts over individual neurons revealed that a single injection of TTX produced a 40% decrease in grain density in ipsilateral NM neurons within 1.5 hr after the TTX injection. However, by 24 hr after a single TTX injection, grain densities were not different on the 2 sides of the brain. Continuous activity blockade for 6 hr caused the cessation of amino acid incorporation in a portion of NM neurons and a 15-20% decrease in the remaining neurons. These changes in amino acid incorporation are comparable to those following complete removal of the cochlea (Steward and Rubel, 1985). We also examined NM for neuron loss and soma shrinkage after blocking eighth nerve action potentials. TTX injected every 12 hr for 48 hr caused a 20% neuron loss and an 8% shrinkage of the remaining neurons. Similar reductions were found following cochlea removal (Born and Rubel, 1985). It is concluded that neuronal activity plays a major role in the maintenance of normal NM neurons. Furthermore, these results suggest that transneuronal morphological changes seen in neurons following deafferentation or alterations of sensory experience are a result of changes in the level of presynaptic activity.