Four siblings with pseudohypoparathyroidism (PHPT) were given parathyroid extract (PTE) for a period of 4 days. The responses of serum and urine calcium, inorganic phosphate, magnesium, and urinary hydroxyproline excretion to these injections were compared to those of five normal subjects and a patient with primary hypoparathyroidism. All patients with PHPT showed a characteristic impairment of the increase in serum calcium and urinary inorganic phosphate excretion. One of the patients, who was receiving 50,000 U daily of vitamin D, showed no greater response to PTE than her untreated siblings. All PHPT subjects exhibited an initial increase in hydroxyproline excretion that, unlike that of the normal subjects, was only transient and fell to only slightly above control levels by the fourth day of PTE injections. In this family, the results indicate that bone retained some of its sensitivity to parathyroid hormone but that the sensitivity was impaired and could not be corrected by administration of large doses of vitamin D.