The cytoarchitectonics of pyramidal neurons in the cerebral cortex of non-lesioned rats can be re-modeled by i.c.v. infusions of nerve growth factor (NGF). 4 months after the application of NGF, the pyramidal neurons in layers III and V of the motor cortex and layer V of the anterior cingulate cortex were analyzed and compared with pyramidal neurons from vehicle-treated rats. NGF-treated brains showed: (1) significant increase in dendritic branching in the basilar fields of the layer V, but not layer III, neurons; and (2) a significant increase in spine density in the terminal, but not proximal, dendritic branches. These findings indicated that, besides its known effects on forebrain cholinergic neurons, NGF produces a very generalized synaptic re-modeling involving the cells responsible for the major output of the cerebral cortex in the intact adult brain.