Rats with either no treatment or administration of exogenous basic fibroblast growth factor (FGF-2) received bilateral medial prefrontal cortical (mPFC) aspiration or sham lesions at postnatal day 3 (P3). FGF-2 was administered either prenatally at embryonic day 15.5 (PreFGF) or, postnatally (PostFGF) for 7 consecutive days beginning 1 day following surgery. As adults, animals were tested behaviorally at spatial navigation (Morris water task), and skilled reaching (Whishaw tray reaching task). Early lesions of the mPFC produced a significant reduction in both brain weight and cortical thickness in adulthood. Behaviorally, mPFC lesions resulted in deficits in the water maze and reaching task. Both pre- and postnatal FGF-2 facilitated recovery in the spatial navigation task. In contrast, FGF-2 was only effective in reducing the deficits in skilled forelimb movements when the FGF was given postnatal (i.e., postsurgery). Prenatal FGF-2 increased brain weight in the lesion animals, whereas postnatal FGF-2 increased cortical thickness in the lesion animals. It thus appears that FGF-2 can facilitate recovery from perinatal cortical injury, whether it is given during the period of neurogeneration (prenatally) or after the injury, although the mechanism of action is likely different for the pre- and postnatal administration.