In order to test the relation between obesity and the secondary hyperparthyroidism found in markedly overweight subjects, 24 morbidly obese patients were studied before and after a weight loss of 35.9 kg obtained by a nutritionally adequate, intermittent very-low-calorie diet. Overweight was reduced from 98 ± 34% to 44 ± 19%. Serum total calcium did not change, but serum ionized calcium (Ca²⁺) increased from 1.22 ± 0.04 mmol/L to 1.25 ± 0.04 mmol/L (P < .001). A corresponding fall was observed in serum parathyroid hormone (s-PTH), which decreased from 47.2 ± 21.7 pmol/L to 35.2 ± 19.4 pmol/L (P = .01). The change of s-PTH was positively associated with the reduction of body weight (r = .50, P < .05) and with the reduction of overweight (r = .55, P < .01). Regarding calcium binding substances, serum albumin remained low. The initially lowered serum phosphate and bicarbonate both rose (P < .001). Plasma lactate and plasma free fatty acids (FFAs) decreased (P < .001). The study supports our hypothesis that the changed profile of calcium complexing anions in obesity interferes with the tubular reabsorption of calcium, which in turn lowers serum Ca²⁺, thus promoting hyperparathyroidism. Along with weight loss, concentrations of calcium complexing anions returns towards normal values and the secondary hyperparathyroidism regresses.