These experiments were designed to determine whether transplants of fetal spinal cord tissue into lesioned spinal cord in newborn rats provide a terrain that supports the growth of serotonergic (5-HT) axons across the site of the lesion. Although descending serotonergic axons can regenerate after chemical lesions in adult animals, they show little regrowth after surgical lesions. In newborn animals, 5-HT axons do not regrow after either chemical or mechanical lesions since the axotomized raphe-spinal neurons die. After partial spinal cord lesions made in developing animals, immature axons can take an aberrant route around the site of the lesion to reach normal target areas. Even these robust, late-growing, uninjured axons, however, are unable to grow through the site of the spinal cord lesion. Immunocytochemical labeling was used to determine if descending serotonergic axons grow into fetal spinal cord transplants, and whether these axons cross the transplant to reach spinal cord levels caudal to the lesion. Spinal cord transection at a mid-thoracic spinal cord level on the day of birth resulted in a dramatic decrease in 5-HT immunoreactivity caudal to the lesion by one day postoperative. 5-HT immunoreactivity caudal to the lesion was abolished by 5 days postoperative and did not return after acute or chronic (6 months) survival periods. When a transplant of fetal spinal cord tissue was placed into the lesion site, 5-HT axons were identified throughout the transplant. At spinal cord levels caudal to the transection and transplant, the serotonergic axons were identified in the host spinal cord in both the white and gray matter. This 5-HT innervation was not confined to spinal cord segments adjacent to the lesion site but extended to spinal cord segments as far as lower lumbar levels. The reinnervation of the host spinal cord caudal to the transection was far less than that seen in unlesioned adult rat spinal cord. Horseradish peroxidase (HRP) injected caudal to the transection and transplant, retrogradely labeled neurons within the medullary raphe nuclei. The HRP and 5-HT results both depended on apposition of the transplant with the rostral and caudal stumps of the host spinal cord; without such apposition, labeling was abolished. These results indicate that the presence of a transplant at the site of the neonatal lesion modifies the environment at the lesion site in such a manner as to support the elongation of identified axons across the site of the lesion and into the host cord caudal to the lesion.