Idiopathic third and sixth cranial nerve neuritis, Abstract Purpose To present cases with idiopathic third and sixth cranial nerve neuritis. Study design Retrospective observational study Methods The results of high resolution pre- and post- cranial nerve magnetic resonance images (MRI) with three-dimensional sequences for visualizing cranial nerves in patients with third, fourth, and sixth cranial nerve palsies who were treated at the Neuro-ophthalmology Department of Samsung Medical Center were reviewed. Patients with cranial nerve enhancement confirmed by experienced radiologists were identified. The medical records of these patients were reviewed, and their demographics, clinical presentations, laboratory results, and clinical outcomes were analyzed. Results Of 265 patients with third, fourth, and sixth cranial nerve palsy, 60 were identified by high resolution MRI as having enhancement of the corresponding cranial nerve. Among these, 17 patients with infiltrative, granulomatous, or tumorous lesions were excluded. In addition, 28 patients with identifiable causes of cranial nerve palsy, such as Miller-fisher syndrome, virus infection, or radiation-induced neuropathy, as well as patients with vasculopathic risk factors, were also excluded. Ultimately, a total of 15 patients with idiopathic third and sixth cranial nerve neuritis were included in this study. The mean age of these patients was 43 ± 15 years. Eight patients had sixth cranial nerve palsy, six third cranial nerve palsy (two partial and four complete), and one patient with complete third and sixth cranial nerve palsy. Nine patients received steroid treatment. Eleven patients recovered fully within a period ranging from a few days to one year. Two patients were much improved up to 1 month after initial presentation, but were then ultimately lost to follow-up. Another patient was lost to follow-up after the initial work-up. The other patient lost to follow-up had partially recovered during the first 6 months. Conclusions We present patients with idiopathic third and sixth cranial nerve neuritis. They tended to respond well to steroid treatment and to have good prognoses. In order to better understand the long-term prognosis of cranial nerve neuritis and possible association with other neurologic disorders, a larger scale and longer-term study is needed.