Basal serum calcium and parathyroid hormone (PTH) levels were measured, and urinary excretion of cyclic adenosine monophosphate (AMP) and phosphate was determined before and after the infusion of 250 U of PTH in four patients with pseudohypoparathyroidism when they were hypocalcemic and again when they spontaneously became normocalcemic. These data were compared to those observed in a group of patients with pseudohypoparathyroidism before and after they became normocalcemic after treatment with vitamin D and calcium. Serum PTH levels were very high in patients with untreated pseudohypoparathyroidism and decreased, although not to normal, when normocalcemia occurred either spontaneously or through treatment. Of the four patients who became normocalcemic spontaneously, basal and PTH-stimulated urinary excretion of cyclic AMP, and clearance of phosphate increased. These changes were all significantly different from the changes which occurred when patients became normocalcemic as a result of treatment with vitamin D anc calcium. The factors which govern the apparent increased renal sensitivity to endogenous and exogenous PTH when normocalcemia develops spontaneously in patients with pseudohypoparathyroidism remain to be explained. However, these changes are dissimilar from those which occur from treatment with vitamin D anc calcium.