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Chronic unilateral motor activity affects the motor output of the contralateral homologous muscle. Such adaptation, or "cross education," indicates an organizational and functional role for the contralateral elements of the central nervous system. In this article, cross education is used as a model to examine this contralateral organization of the human central nervous system. The possibility of whether there are direct changes in the excitability of transcallosal paths and whether, linked to these changes, there are indirect modulations in the excitability of contralateral corticospinal projections is examined. The paper also explores the possibility that there is a spinal component in cross education. The study observed that there is an abundance of evidence to suggest that chronic activation of muscles on one side of the body produces adaptations in the same muscles on the other side of the body in healthy adults as well as in individuals with a variety of pathologies. Data inferred from cross-sectional studies make it likely that interhemispheric and spinal paths both contribute to cross education. Although interhemispheric callosal paths in humans are moderate to dense with the majority of the interhemispheric connections being inhibitory, the connections between the homologous muscles tend to be excitatory, providing a neuroanatomical basis for cross education. The possibility exists that the effects of unilateral practice on interhemispheric inhibition and on the excitability of the contralateral corticospinal projections are linked, and these effects are graded according to the nature of muscle activation. The possibility also exists that cross education is mediated by cross-spinal paths. Cutaneous stimulation appears to exert strong excitatory effects on contralateral motor neurons. In total, an understanding of interhemispheric interactions in the human motor cortex may shed light on the mechanisms of motor learning and the coordination of bilateral movements and improve methods of therapeutic rehabilitation.