Clinical and MRI investigations were carried out on 27 patients with acquired pendular nystagmus in an attempt to delineate possible sites of lesions responsible for pendular nystagmus and mechanisms underlying the frequent ocular disconjugacy of this nystagmus. The aetiologies were multiple sclerosis (n = 21), brainstem stroke (n = 3) and other neurological conditions. In at least 59% of the patients, pendular nystagmus appeared >1 year after the first symptom of the disease. Patients' MRIs were characterized by multiple areas of abnormal signal and were analysed statistically to identify areas where lesions overlapped significantly between patients. Statistically significant overlap occurred in areas containing the red nucleus, the central tegmental tract, the medial vestibular nucleus and the inferior olive. Patients with horizontal pendular nystagmus showed predominantly pontine lesions whereas patients with torsional pendular nystagmus showed predominantly medullary involvement. The nystagmus was conjugate in 15 patients and disconjugate in amplitude or direction in 12. Internuclear ophthalmoplegia or asymmetrical visual acuity occurred in similar proportions in both groups. Patients with conjugate pendular nystagmus had a higher incidence of symmetrical, ‘mirror image’ lesions on MRI than patients with disconjugate nystagmus. The abundance of abnormal MRI signals in our sample suggests that large or multiple structural lesions may be required to elicit pendular nystagmus, predominantly in the pons but also in the midbrain and medulla. The involvement of structures projecting to the inferior olive supports the hypothesis that oscillatory properties of olivary neurons causes the rhythm of pendular nystagmus. The delay observed between the onset of the underlying disease and the pendular nystagmus supports a mechanism operating via neural deafferentation. Disconjugancies in pendular nystagmus cannot be explained on the basis of the associated internuclear ophthalmoplegias nor on the basis of asymmetrical visual acuity. The association between symmetrical MRI lesions and conjugate nystagmus suggests that asymmetrical damage to brainstem structures concerned with binocular alignment may underlie disconjugate pendular nystagmus.