One man and three women with hypothalamic hypothyroidism are described; they had isolated thyrotropin-releasing hormone deficiency, otherwise normal pituitary function, and no identifiable central nervous system anatomic abnormality. Serum thyrotropin levels were low and thyrotropic response to thyrotropin-releasing hormone was uniformly present, consistent with a hypothalamic cause of hypothyroidism. In two patients, hypothyroidism was transient and spontaneously resolved; in one of them, it was recurrent. Because hypothalamic hypothyroidism is mild and potentially reversible, it is suggested that such patients have follow-up evaluation before therapy is initiated in order to avoid unnecessary treatment.