The rat red nucleus was investigated as a model for the study of synaptic remodelling following specific deafferentation. The normal neonatal and adult afferent projections from the deep cerebellar nuclei and the sensorimotor cortex were studied using anterograde and retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA), as well as retrograde transport of the fluorochromes Fast Blue and Nuclear Yellow. To examine the normal synaptology of the red nucleus, the anterogradely transported HRP-WGA was visualized ultrastructurally. The rat red nucleus receives topographically organized afferents which may be characterized by their specificity in location at the cellular level. The evidence provided also indicates the existence of a two-neuron cerebello-rubro-cerebellar loop between the nucleus interpositus and the red nucleus.;Specific neonatal deafferentation of the red nucleus induced the formation of aberrant afferent fibers from both normally crossed (i.e. cerebellorubral) and uncrossed (i.e. cerebrocorticorubral) projections to this nucleus, thereby replacing the lesioned pathway. Moreover, the normal topographic and somatotopic specificity was maintained in both of the aberrant cortical and cerebellar projections.;The specificity of synaptic localization in the aberrant rubral afferent projections was studied ultrastructurally. In neonatally hemicerebellectomized adult rats, both the normal contralateral and aberrant ipsilateral interpositorubral projections synapsed on somatic and proximal dendritic membrane of magnocellular neurons. Similarly, bilateral projections from the unablated nucleus lateralis terminated on small to medium sized dendrites of parvocellular neurons. In addition, following neonatal sensorimotor cortical lesions, the remaining sensorimotor cortex projected bilaterally to terminate on distal dendrites of parvocellular neurons.;In summary, the present study demonstrated that, following neonatal deafferentation, the neuroanatomical plasticity in the rubral afferent projections displayed several degrees of specificity which may provide the structural basis for recovery following lesions