Eight patients with intracranial malignancies or vascular lesions and sixth nerve palsies were treated with botulinum toxin chemodenervation of the antagonist medial rectus muscle. Primary deviation ranged from 20 to 75 prism diopters (pd) of esotropia. Six were treated acutely (within 3 months of onset) and two, which demonstrated partial recovery of lateral rectus function but with residual esotropia and diplopia, were treated after 6 months. After a mean follow-up of 20.6 months, seven were diplopia-free with excellent rotations. Five had complete resolution of the esotropia and diplopia, with near complete recovery of abduction. One had 6 pd residual esotropia, while another, whose sixth nerve had been resected, required a modified Jensen procedure, resulting in full rotations. The single case of bilateral sixth nerve palsy had a functional improvement but was lost to follow-up. One patient had a vertical strabismus induced with the injection and had a gradual return of the esotropia.