Pseudotumor cerebri occurs in many diverse endocrine and nonendocrine disorders. We report what we believe is a new association following initiation of thyroxine (T4) replacement in hypothalamic hypothyroidism, as well as another occurrence following T4 replacement in primary hypothyroidism. The less than benign clinical course reported in these two patients suggests the need for careful neurologic and funduscopic evaluation during the initial months of T4 replacement in all cases of hypothyroidism.