Despite important physiological functions, the fluctuations in plasma ionized calcium concentrations [Ca++] after major thermal injury have not been defined. Measurements of [Ca++] were undertaken in 25 patients of age ranging from 6–75 years, with body surface area burns of 25–85%. Plasma total calcium [Ca], inorganic phosphorus [Pi] and magnesium [Mg++] were also followed. Urinary excretion of the same ions was quantified in nine patients for the first 6 days postburn. The control group consisted of 12 patients who had sustained a similar injury at least 16 months earlier. Significantly low [Ca++] persisted throughout the observation period, despite an average replacement of 0.2 mM/kgμday of CaCl2. The initial hypophosphatemia and hypermagnesemia tended toward normal during the latter phase of the injury. Urinary excretion of the cations was not significantly elevated in the first 6 days postburn. The usual reciprocal relationship between [Ca] and [Pi] was not evident, and there was no correlation between [Ca++] and the size of burn. The use of McLean-Hastings nomogram poorly predicted the [Ca++] from [Ca]. Our data indicate that marked alterations in [Ca++] homeostasis occur after thermal injury. The etiology of hypocalcemia remains to be elucidated; the physiological consequences in terms of hemodynamic function deserve further study.