The authors describe five patients with trochlear nerve palsy and MS to characterize this rare association. In two patients, trochlear nerve palsy was the initial clinical manifestation of MS. In the other three patients, this sign occurred after previous neurologic events. MRI did not identify a lesion of the fourth nerve nucleus or fascicle. Ophthalmoplegia resolved within 2 months in four of the five patients. A reason this association is rare is that the fascicular course of the trochlear nerve is exposed to little myelin.