We have shown previously that epidermal growth factor (EGF) plus fibroblast growth factor (FGF2) expands the neural precursor cells in the ependyma of the normal adult rat spinal cord in vivo. To investigate the therapeutic effect of these factors on spinal cord injury (SCI), we administered EGF, FGF2, EGF plus FGF2, or artificial cerebrospinal fluid (aCSF) intrathecally (15 ng/h of EGF or FGF2) for 3 or 14 days after mild (2.4-g) or moderate (20-g) clip compression injury at T1 in adult rats. Histological and functional assessments were used to evaluate the therapeutic effects. The EGF plus FGF2 group, which received these agents for 14 days, showed better functional recovery than the aCSF group 42 days after moderate SCI (p < 0.05). At 14 days, the EGF plus FGF2 group showed a much greater expansion of ependymal cells and astrocytes compared to the other groups, and there was evidence for extensive migration of ependymal cells into the surrounding injured cord. These mitogens did not significantly enhance nestin expression in the ependymal layer or alter the expansion of oligodendrocyte precursor cells or microglia/macrophages, and dividing cells did not show the neuron-specific marker NeuN except immediately adjacent to the ependyma. The exact mechanism for improved functional recovery after EGF plus FGF2 is not known.