The purpose of this study is to review the incidence of contrast enhancement of the trigeminal nerve on magnetic resonance imaging (MRI) in a large cohort of patients with multiple sclerosis (MS). MRI scans of 851 MS patients participating in a phase III clinical trial were reviewed for the presence of gadolinium enhancement on postcontrast T1-weighted images. If enhancement was present, it was documented whether this involved only the proximal or also the distal part of the fifth nerve, and whether the abnormality was unilateral or bilateral. In 24 (2.8%) patients, enhancement of the trigeminal nerve was observed, and was bilateral in 16 (66.7%) of those. In 19 (79.2%) patients with abnormal nerves, enhancement extended to the distal part of the trigeminal nerve (into Meckel's cave). The results of this study indicate a high, probably clinically silent, incidence of trigeminal nerve demyelination in MS and frequent involvement of the peripheral type of myelin in MS.