Introduction: Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign, inherited condition caused by inactivating mutations in the calcium-sensing receptor (CASR) gene. Both FHH and primary hyperparathyroidism (PHPT) are characterized by elevated P-calcium, normal or elevated plasmaparathyroid hormone (P-PTH), and typically normal renal function. In PHPT, vitamin D metabolism is typically characterized by low plasma levels of 25-hydroxyvitamin D (25OHD), and high plasma levels of 1,25-dihydroxyvitamin D (1,25(OH) 2 D). In FHH, the vitamin D metabolism is not very well known. Objective: To compare and evaluate plasma 25OHD, 1,25(OH) 2 D, and PTH in FHH and PHPT. Design: Cross-sectional study. Materials: About 66 FHH patients with mutations in the CASR gene, 147 patients with surgically verified PHPT, and 46 controls matched to FHH patients according to age (G5 years), sex, and season. All patients had a P-creatinine !140 mmol/l. Methods: We measured P-calcium, P-Ca 2C , P-albumin, P-creatinine, P-phosphate, P-magnesium, and P-PTH by standard laboratory methods. P-25OHD and P-1,25(OH) 2 D were measured by RIA or enzyme immunoassay. In FHH, all protein-coding exons in the CASR gene were sequenced and aligned to GenBank reference sequence NM_000388.2. Results: PHPT patients had higher body mass index (2p!0.01), together with higher P-PTH (2p! 0.01) and P-1,25(OH) 2 D (2p!0.01) compared with FHH patients. The groups had similar levels of P-Ca 2C and of P-25OHD. The phenotypic expression of the CASR mutations (as determined by the degree of hypercalcemia) did not influence the levels of P-1,25(OH) 2 D. Conclusion: Even though P-calcium and P-25OHD were comparable, P-1,25(OH) 2 D and P-PTH differed between FHH and PHPT.