The association between hypogonadotropic hypogonadism and multiple CNS lesions in a variety of disorders suggests a possible causative link between these clinical findings. Neural afferent input into the hypothalamus from higher CNS centers modulates GnRH secretion and derangements of these neural pathways could potentially result in diminished gonadotropin secretion and hypogonadism. This report describes a patient with multiple CNS defects secondary to Moebius syndrome and hypogonadotropic hypogonadism whose clinical features support the hypothesis that his CNS and endocrine defects may be causally associated. Comprehensive clinical evaluation in this patient revealed severe mental retardation; cranial nerve palsies; motor, reflex, and gait disturbances; and sexual infantilism secondary to hypogonadotropic hypogonadism. An MRI of the brain revealed atrophy or hypoplasia of the third cranial nerve and the olfactory gyri. Numerous syndromes including the Moebius syndrome are now described in which hypogonadotropic hypogonadism and CNS defects are associated. Detailed neuroanatomic and embryologic studies have demonstrated the important functional interrelationships between higher central nervous system centers and the hypothalamus. Taken together, these findings provide support for the causative association of multiple CNS defects and hypogonadotropic hypogonadism.