Unilateral eyelid suture, a model for amblyopia induced by congenital cataract, produces shrinkage of the deprived eye's ocular dominance columns in the striate cortex. Loss of geniculocortical projections are thought to account for the poor vision in the amblyopic eye. It is uncertain whether ocular dominance columns become shrunken in other forms of amblyopia. We examined the striate cortex in a pigtailed macaque with natural anisometropia discovered at age 5 months. Amblyopia in the left eye was documented at 1 year by behavioral testing. At age 6 years, the left eye was injected with [3H]proline and the striate cortex was processed for autoradiography and cytochrome oxidase (CO). The ocular dominance columns in layer IVc labelled with [3H]proline were normal. CO staining showed a novel pattern of thin dark bands in layer IV. These bands occupied the core zones at the center of the ocular dominance columns. Their appearance resulted from relative loss of CO activity along the borders of the ocular dominance columns, regions specialized for binocular processing. These findings indicate that not all forms of amblyopia are accompanied by shrinkage of ocular dominance columns. The unusual pattern of CO staining in layer IVc reflected a subtle alteration in metabolic activity which may have resulted from impairment of binocular function in anisometropic amblyopia.