Five full-term infants with birth weights appropriate for gestational age presented with hypocalcemic tetany at 5 to 9 days of age. All infants had been fed Similac 20, a cow milk formula. Initial mean serum calcium (Ca), phosphorus (P), and magnesium (Mg) levels of the tetanic infants were 6.8, 9.5, and 1.6 mg/dL, respectively. The mean serum parathyroid hormone (PTH) level was elevated at 79 mu LEq/mL (adult normal values, less than or equal to 57 mu LEq/mL). Following restoration of normocalcemia with Ca supplements, feeding was reinstituted with Similac 20 in two infants and Similac PM 60/40 in three infants. Serum biochemical and hormonal values were compared with those of 18 exclusively breast-fed infants followed up from three weeks to six months and 14 Similac 20-fed full-term infants followed up from one week to six months. In tetanic infants, serum Ca concentrations became elevated (10.4 +/- 0.05 mg/dL; mean +/- SEM) by six weeks (vs 9.2 +/- 0.3 mg/dL in breast-fed infants) (P less than .001) and serum Mg concentrations (2.26 +/- 0.01 mg/dL) by four weeks (vs 1.92 +/- 0.07 mg/dL in breast-fed infants) (P less than .01). Mean serum P concentrations declined progressively. Mean serum PTH concentrations were elevated and ranged from 74 to 143 mu LEq/mL at two to 16 weeks (vs mean 28 to 35 mu LEq/mL in breast-fed infants (P less than .0001). In 14 formula-fed-nontetanic full-term infants, serum PTH concentrations were intermediate between formula-fed-tetanic and breast-fed infants, mean serum Ca concentrations ranged from 10.2 to 10.4 mg/dL, and mean serum P concentrations declined from 8.3 to 7.1 mg/dL. We speculate that acute hypocalcemic tetany in the study infants was induced by the relatively high P load in cow milk formulas (vs human milk); with the continued P load, secondary hyperparathyroidism continued, maintaining P, Ca, and Mg homeostasis.