ABSTRACT Hypothalamic-pituitary function and gonadal histology and responsiveness have been assessed in three patients with isolated deficiency of gonadotrophin secretion. Gonadotrophin secretion was uniformly reduced and sex steroid excretion markedly impaired in all three cases. Biopsy of the gonad showed immature glands and no increment in steroid excretion resulted from stimulation using human chorionic gonadotrophin. No response in gonadotrophins to clomiphene occurred in 2 of the 3 patients tested. Whereas normal ACTH and adrenal response to hypoglycaemic stress and metopirone was shown in 2 of the 3 cases, the increment in growth hormone secretion was reduced. Following sex steroid therapy, the growth hormone response was improved and increased ACTH release during hypoglycaemia was observed in one patient. No change in gonadotrophin secretion occurred during longterm sex steroid therapy.