Discussed in this paper is the application of a neurobehavioral, functional systems approach to the understanding of verbal-motor integration difficulties experienced by persons with Down syndrome. In initial work, noninvasive neuropsychological techniques were used to examine both the similarities and differences in cerebral organization and perceptual-motor behavior between persons with Down syndrome and control subjects of the same chronological and/or mental age. This group-difference research led to the development of a specific model of brain-behavior relations in persons with Down syndrome. The main feature of the model is the neuroanatomical disconnection of the brain areas responsible for speech perception and movement organization. The basic tenets of the model are described, and efforts to test and refine it are discussed. This approach exemplifies how general neurobehavioral rules and principles can be harnessed to understand the exceptions to those rules often encountered with special populations.