The present investigation offers a basis for demonstrating that the cerebral cortex can be directly accessed through the immune system. This project was undertaken to provide a necessary step in confirming that the localized, deficient area of the cerebral cortex in the congenitally athymic nude mouse is related to the thymus, a gland necessary for the development of T-cells and the regulation of the neuro-endocrine system. We report that thymus engraftment, confirmed by reconstitution of CD4 and CD8 T-cells, in 30-day-old congenitally athymic female mice reverses deficiencies in the frontal cortex by day 60. A concomitant increase in serum prolactin was observed in thymic-grafted nude mice, suggesting a role by which prolactin may produce the morphological changes observed in the cerebral cortex.