Miller-Dieker syndrome (MDS) is a prototype of brain malformations characterized by abnormal neuronal migration. To clarify the pathomechanisms underlying these anomalies, we performed immunohistochemical studies using specific antibodies against the protein product of LIS-1, the candidate gene responsible for the MDS phenotype. The LIS-1 protein was present abundantly and ubiquitously in normally developing brains. Loss of LIS-1 immunoreactivity was observed in brains with MDS, but not in brains with other malformations, such as isolated lissencephaly, holoprosencephaly, Fukuyama-type congenital muscular dystrophy, and Zellweger syndrome. These results suggest that the pathomechanism underlying abnormal neuronal migration in MDS may be specific to this particular type of malformation.