A 41-year-old negro man with fatigue, weight loss, decreased libido, impotence, polyuria, and polydipsia of 5 years' duration is described. Symptoms had begun 2 months after a prolonged, high-altitude flight. His prostate and testes were abnormally soft. Visual fields and chromosome analysis were normal. Testicular biopsy showed no spermatogenesis, with generalized tubular and interstitial atrophy. Hemoglobin electrophoresis showed A and S hemoglobins. Skull X rays showed suprasellar calcification, but carotid arteriograms were normal. Craniotomy showed no evidence of tumor or other lesions. The response of his low urinary steroid excretion to adrenocorticotrophic hormone and metyrapone (Metopirone®) indicated secondary hypoadrenalism. Plasma growth hormone did not increase with insulin-induced hypoglycemia. Thyroid function was at the lower limits of normal. The values for serum and urine osmolality after overnight fasting, saline infusion, vasopressin (Pitressin®) infusion, and prolonged water deprivation were diagnostic of pituitary diabetes insipidus. Review of the English literature showed two patients with sickle cell trait and pituitary infarction proved at autopsy. Since the nephropathy of sickle cell trait is vasopressin-resistant, vasopressin-responsive hyposthenuria in persons with S hemoglobin suggests pituitary involvement. A causal relationship between this patient's sickle trait and generalized hypopituitarism is suggested.