The Small eye (Sey) gene, which has been mapped to chromosome 2 in the mouse, is known to cause variable malformations of the eye and nose. The effect of the gene in the heterozygous state is mainly on the eye. A combined electron microscopy and morphometric analysis of the optic nerve in adult littermates with a normal (+/+) and heterozygous mutant (Sey/+) genotype was carried out. The optic nerve could be dissected from the posterior pole of the eyeball to the optic chiasma in all the mice examined. The results of morphometric analyses carried out in this study show that the Sey gene indirectly affects the normal morphogenesis of the optic nerve in the heterozygous mutant Sey male mouse to a significant degree compared with its male normal littermate. The heterozygous mutant Sey female mouse is also affected, but not significantly so when compared with its normal female littermate. The mean nerve cross-sectional area and mean nerve fibre counts for the Sey strain are lower than those observed in other strains of mice that have been studied. The nerve fibre densities and the spectrum of nerve fibre sizes encountered are, however, similar to those seen in other strains of mice. We believe that the findings indicate that the smaller mean nerve fibre counts observed in the heterozygous mutant (Sey/+) mice compared to their normal (+/+) siblings is unlikely to have resulted from primary retinal dysgenesis, but is a consequence of the reduced size of their neural retina, and total retinal ganglion cell population.