AIM: To further define the pathogenesis of infantile hypocalcemia, the prevailing vitamin D status, and treatment outcomes. METHODS AND RESULTS: Of the 23 infants admitted with infantile hypocalcemia, 21 had biochemical evidence of hypocalcemia and hyperphosphatemia and the other two had isolated hypocalcemia. The majority of these infants had relatively low serum intact parathyroid hormone responses against the backdrop of hypocalcemia. Thirteen (56.5%) of these infants had low 25-hydroxyvitamin D (25-OHD) levels, of whom 69% were Hispanic and 23% were African American. Infantile serum vitamin D status reflected that of the mother in all the 16 instances in which it was measured. Treatment with calcitriol hastened recovery from hypocalcemia in our series. CONCLUSIONS: Relative hypoparathyroidism is the etiology in the majority of cases of late onset and early infantile hypocalcemia. We identified vitamin D deficiency in a significant percentage of infants with hypocalcemia, especially Hispanics and African Americans. Maternal 25-OHD concentrations should be ascertained if the infant has low 25-OHD levels.