Brain development in humans is remarkably resistant to permanent damage from protein-energy malnutrition. However, specific nutrients have crucial roles. Iodine deficiency is the most important and widespread nutrient deficiency; it causes endemic cretinism, associated with deaf-mutism and cerebral palsy. Iodine deficiency during pregnancy causes both maternal and fetal hypothyroxinemia, resulting in irreversible impairment of brain development at a critical stage. Neuropathological data place this after 14 wk, perhaps continuing through the third trimester. Gross brain structure, including the gyral pattern of the cerebral cortex, develops normally; the insult affects neuron and dendrite growth. Recent magnetic-resonance-imaging (MRI) images of neurological cretin brains show remarkably normal appearance except for gliotic lesions of the globus pallidus, correlating with the proximal motor rigidity seen clinically. Myxedematous cretinism is paradoxical in showing more severe hypothyroidism and growth failure, yet better intellectual, motor, and hearing function; these observations implicate a second independent factor in its pathogenesis.