Neurons depend upon the processes of axonal and transneuronal transport for intra- and intercellular communication and trophic support. Experimental studies in the last decade have elucidated the mechanisms underlying these processes, and provided evidence for their role in the spread of viral and toxic diseases through the nervous system. Recent advances in neuroanatomy, and in the pathological study of certain degenerative conditions, such as Alzheimer's disease, suggest that the same principles may underlie the anatomical specificity of cell loss in a variety of system degenerations. In Alzheimer's disease, as well as in olivo-ponto-cerebellar atrophy, progressive supranuclear palsy, amyotrophic lateral sclerosis, primary autonomic failure of the Shy-Drager type, and other system degenerations, the main feature that marks the affected populations of neurons is their anatomical interconnectivity. We consider here the possibility that, in these conditions, the processes of axonal and transneuronal transport may subserve the transmission from neuron to neuron of a toxic or infectious agent, or alternatively that the diseases may result from the failure of normal transport of a trophic agent. This hypothesis not only provides a unifying framework in which to view a variety of seemingly disparate conditions, but also suggests certain approaches to identifying the causative agents.