The expression of mRNA encoding the growth associated protein, GAP-43, was investigated in rat hypoglossal motor neurons when the hypoglossal nerve was either resected or crushed unilaterally. For the detection of GAP-43 mRNA, a histochemical in situ hybridization method. using an alkaline phosphatase labeled probe, was used. The temporal profiles of GAP-43 mRNA expression were not identical following the two types of injuries. Increased expression in the hypoglossal nucleus contralateral to the injured nerve was observed from 1 day to 4-6 weeks after nerve crush, but lasted up to 7-8 weeks after resection. The magnitude and duration of increased GAP-43 mRNA expression were significantly greater following resection than crush injury. Local treatment with vinblastine, which is known to disturb the fast axonal flow by depolymerizing tubulin, also induced GAP-43 mRNA expression. The patterns of gene regulation following these nerve injuries may be due to the extent of nerve damage, to tubulin disturbance, or to some other factors derived from outside the nerve.