To aid in development of chronic stage treatments for sensorimotor deficits induced by ischemic stroke, we investigated the effects of GABA antagonism on brain structure and fine skilled reaching in a rat model of focal ischemia induced via cortical microinjections of endothelin-1 (ET-1). Beginning 7 days after stroke, animals were administered a gamma-aminobutyric acid (GABA A ) inverse agonist, L-655,708, at a dose low enough to afford α5-GABA A receptor specificity. A week after stroke, the ischemic lesion comprised a small hypointense necrotic core (6 ± 1 mm 3 ) surrounded by a large (62 ± 11 mm 3 ) hyperintense perilesional region; the skilled reaching ability on the Montoya staircase test was decreased to 34% ± 2% of the animals' prestroke performance level. On L-655,708 treatment, animals showed a progressive decrease in total stroke volume (13 ± 4 mm 3 per week), with no change in animals receiving placebo. Concomitantly, treated animals' skilled reaching progressively improved by 9% ± 1% per week, so that after 2 weeks of treatment, these animals performed at 65% ± 6% of their baseline ability, which was 25% ± 11% better than animals given placebo. These data indicate beneficial effects of delayed, sustained low-dose GABA A antagonism on neuroanatomic injury and skilled reaching in the chronic stage of stroke recovery in an ET-1 rat model of focal ischemia.