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/kg.day of CaCl2. The initial hypophosphatemia and hypermagnesemia tended toward normal during the latter phase of the injury. Urinary excretion of the 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.