The long-term morphological consequences on laminar thickness and neuron survival were assessed in cerebral cortical area PMLS following excision of visual cortical areas 17, 18, and 19 from adult and adolescent cats and from neonatal kittens. Following excisions from kittens, layers III, V, and VI in area PMLS were reduced in thickness and there was a significant loss of neurons from layers III and VI. Following excisions from adolescent cats, layers V and VI were thinner than normal, whereas excisions from adult cats resulted in a detect able thinning only of layer V and no neuron loss from any layer. In a parallel study, the configuration of projections between area PMLS and areas 11, 18, and 19 in adult cats and newborn kittens was analyzed and related to the patterns of neuron survival and death in area PMLS following the excisions. In adult cats, projections from areas 17, 18, and 19 terminate in all layers, but they are heaviest into layer III in area PMLS. Layers III and VI contain the largest number of neurons that form the origin of the reciprocal projections back to areas 17, 18, and 19. In area PMLS of the newborn kitten, the laminar distribution of cells projecting to areas 17, 18, and 19 resembles the pattern in the adult cat, although the laminar pattern of the terminations is poorly differentiated. The pattern of cell death following the excisions from the kittens can be most easily explained on the basis of the mature configuration of the reciprocal pathways and on the neurons maturational status at the time areas 17, 18, and 19 were removed. Thus, immature cortical neurons that are deprived of their targets and inputs undergo degenerative changes. These changes are most severe in infancy, and they can be predicted on the basis of the final patterns of projections the neurons would have developed with the damaged region. This loss of neurons in early-lesioned animals in regions of cortex anatomically connected to the damaged tissue implies that there may be cognitive deficits associated with the secondary degeneration in addition to the deficits caused by the primary lesion.