Joubert syndrome is a rare autosomal-recessive condition characterized by early hyperpnea and apnea, developmental delay, and truncal ataxia. We previously described key ocular motor signs in Joubert syndrome and the molar tooth sign resulting from dysplasia of the isthmic segment of the brain stem, superior cerebellar peduncles, and vermis. In this study, we obtained clinical and developmental data in 61 cases, and radiologic data in 46 of these, to determine the prevalence of the molar tooth sign in a large sample, and to ensure that magnetic resonance images obtained for study were representative of the Joubert syndrome population at large. We studied the morphology of the isthmic segment of the pontomesencephalic junction, the segment of the brain stem derived from the primitive isthmus. Portions of the cerebellum analyzed included the superior cerebellar peduncles, the anterior and posterior lobes of the vermis, and the flocculonodular lobe. In one case, autopsy of the brain was performed. The average age at diagnosis was 33 months. All patients were hypo-tonic and developmentally delayed. The molar tooth sign was present in 85% of cases with 13% of these showing additional malformations. All patients without the molar tooth sign had other mimicking conditions such as neocerebellar dysgenesis, isolated vermian atrophy, cerebellar aplasia, and cystic dilation of the cisterna magna. Autopsy showed aplasia of the cerebellar vermis with dysplasia of the dentate nucleus, elongated locus coeruleus, and marked dysplasia of the caudal medulla. A better understanding of the clinical, radiologic, and pathologic features of Joubert syndrome should help uncover the genetic basis for the syndrome. (J Child Neurol 1999;14:368-376).