This study represents a first effort to characterize the growth and development of murine trisomy 16 neurons using single-cell neuron culture techniques. Murine trisomy 16 is a model for the human Down syndrome, or trisomy 21. Both show similar nervous system abnormalities including decreases in cerebellar size and in numbers of cerebellar neurons. Trisomy 16 cerebellar neurons cultured from 17-gestational day conceptuses grew less extensive neuritic arbors than normal neurons. Unlike controls, the individual neurites of the trisomic neurons were not clearly distinguishable as axons or dendrites over the 10 day period that they were observed. The trisomic neurons were characterized by diminished levels of microtubules, abnormally shaped mitochondria, and the presence of dense bundles of abnormal filaments that were not observed in any of the normal littermate neurons.