An antisense oligonucleotide to brain-derived neurotrophic factor (BDNF) was delivered by osmotic mini-pump at a 1 mM concentration via a cannula into the ipsilateral vestibular nucleus complex from 15 to 56h following unilateral labyrinthectomy in guinea pigs. Compared with the control groups, vestibular compensation of roll head tilt was significantly delayed (p < 0.05), while compensation of spontaneous nystagmus and yaw head tilt was unaffected. These results suggest that neurotrophins such as BDNF may be involved in specific aspects of the vestibular compensation process.