Neurotoxic injury of the caudate-putamen and lateral globus pallidus unilaterally initiated transneuronal degeneration of neurons in the ipsilateral substantia nigra reticulata (SNR). Quantification of SNR neurons using unbiased stereology demonstrated that neuron loss began 4 days after the initial striatal lesion, followed by significant loss (50%) at 6 days and a plateau at 8 days. Analysis at the light and ultrastructural levels revealed morphological changes consistent with a type of programmed cell death. These temporal and histological results refine an in vivo model in which to explore mechanisms of delayed neuronal degeneration.