Rats with unilateral or bilateral removal of the cortex anterior to the bregma (frontal cortex) in adulthood were compared behaviorally and neuroanatomically to (1) rats with similar removals at 1 or 10 days of age, (2) rats with staged bilateral removals having a unilateral frontal lesion at 1 day and a second lesion at 10 days of age, and (3) rats that were hemidecorticated at 1 day of age. Age at lesion, unilaterality of lesion, and size of lesion interacted to alter brain development and behavior in different ways. Bilateral frontal lesions at 1 day of age produced a very small brain and thin cortex, and were associated with poor spatial learning. Similar removals at 10 days postnatal allowed sparing of spatial learning, but the cortex was still thinner than normal. Unilateral frontal lesions at any age produced similar behavioral effects, which were smaller than after bilateral lesions, and the neonatal lesions produced thinning of the ipsilateral cortex. Staged lesions allowed partial sparing of behavior, but there was cortical thinning equivalent to that after 1- or 10-day lesions in the respective hemispheres. In contrast to the effect of unilateral neonatal frontal lesions, which have little effect on the contralateral cortex, neonatal hemidecortication increased cortical thickness in the opposite hemisphere. These results imply that the effects of cortical injury in infancy vary with age, unilaterality of the lesion, and lesion size.