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. (C) 1998 Elsevier Science B.V. All rights reserved.