The purpose of this study was to examine the effect of the microphthalmia gene on pre-natal optic nerve development in the mouse. Coronal serial sections of wild-type, heterozygote and homozygous microphthalmic embryonic optic nerves are examined throughout gestation. No obvious morphological abnormality was identified in the heterozygote. The microphthalmic optic stalk/nerve was larger than that of the wild-type and heterozygote and there was persistence of the optic stalk throughout gestation. This was due to a high mitotic rate and reduced cell death in the dorsal layer of the microphthalmic optic stalk as well as persistence of the optic ventricle throughout gestation. The latter was associated with persistence of intermediate-type junctions between the neuroepithelial cells lining the ventricle and failure of the cells on the dorsal aspect of the distal stalk to degenerate. Possible mechanisms for the disappearance of the optic ventricle in the normal optic stalk are suggested.