BACKGROUND AND PURPOSE: gamma-Hydroxybutyrate (GHB), a natural metabolite of gamma-aminobutyric acid and a drug used in humans to promote slow-wave sleep and treat narcolepsy, has been suggested to protect against ischemic stroke at high doses. This study aimed to assess recovery-promoting effects of GHB at a low dose similar to that used in patients. METHODS: Adult mice, subjected to 30 min of intraluminal middle cerebral artery occlusion, were intraperitoneally treated with GHB (100 mg/kg, twice/day, 8 h apart) or saline for 10 days. Motor recovery was evaluated by the grip strength test. The brain lesion was assessed by cresyl violet and NeuN staining 5 weeks after stroke. Expression of neuroplasticity-related genes (GAP43, c-jun, neurocan and ephrin B1) was analyzed by Taqman real-time PCR. RESULTS: GHB-treated mice regained their body weight faster and recovered grip strength (3 weeks after stroke) more quickly than saline-treated mice. This was noteworthy as GHB did not influence ischemia-induced brain injury, as revealed by cresyl violet and neuronal staining. The Taqman PCR assay revealed a decreased expression of c-jun and neurocan in the ischemic striatum of GHB-treated mice in comparison to saline-treated mice. CONCLUSION: GHB at a low dose accelerates neurological recovery following ischemic stroke. Further studies are necessary to determine the potential relationship between GHB, neuroplasticity, sleep and stroke recovery.