To investigate the neural basis for functional recovery of the cerebral cortex following spinal cord injury, we measured the expression of growth-associated protein 43 (GAP-43), which is involved in the process of synaptic sprouting. We determined the GAP-43 mRNA expression levels in the sensorimotor cortical areas of macaque monkeys with a unilateral lesion of the lateral corticospinal tract (l-CST) at the C4/C5 level of the cervical cord and compared them with the levels in the corresponding regions of intact monkeys. Lesioned monkeys recovered finger dexterity during the first months after surgery, and the GAP-43 mRNA levels increased in layers II-III in primary motor areas (M1), bilaterally. Double-labeling analysis of the lesioned monkeys showed that GAP-43 mRNA was expressed strongly in excitatory neurons but only rarely in inhibitory interneurons. Expression also increased in the medium-sized (area, 500-1,000 microm(2)) and large pyramidal cells (area, >1,000 microm(2)) in layer V of the bilateral M1. The increased expression of GAP-43 mRNA in the M1 contralateral to the lesion was more prominent during the early recovery stage than during the late recovery stage. In addition, GAP-43 mRNA increased in layers II-III of both the contralesional ventral premotor area and the primary somatosensory area. These results suggest that GAP-43 is involved in time-dependent and brain region-specific plastic changes after l-CST lesioning. The expression patterns imply that plastic changes occur not only in M1 but also in the broad associative cortical network, including the ventral premotor and primary sensory areas.