Infantile autism is a behavioral syndrome consisting of specific disturbances of social relating and communication, language, response to objects, sensory sensitivity and motility. The uniqueness of this syndrome suggests one underlying pathophysiologic mechanism, although multiple etiologies, which could activate or replicate such a mechanism, have been demonstrated. Review of considerable experimental evidence and clinical observation suggests that the symptomatology of autism, including the disturbances of social relating and communication, can best be explained as a disorder of sensory modulation. This in turn suggests a neurophysiologic mechanism consisting of dysfunction of a cascading series of neurophysiologic levels or interacting neuronal loops in the brainstem and diencephalon which subserve modulation of sensory input. Some of those same systems modulate motor output in response to sensory input, and their dysfunction may release the abnormal perseverative motility of infantile autism. Other experimental evidence and clinical observations stress the language deficits of autism and implicate dysfunction of cortical structures. Brainstem and diencephalic centers project rostrally to telencephalic structures and these, in turn, modify brainstem and diencephalic function. Theories of rostrally and caudally directed sequences of pathoneurophysiologic contributions to the system dysfunction in autism are compared. It is concluded that the symptoms of autism can best be explained in terms of dysfunction of brainstem and related diencephalic behavioral systems and their elaboration and refinement by selected higher neural structures.