Many studies showed an increased occurrence of primary hyperparathyroidism during lithium therapy. We studied 53 patients receiving lithium therapy prospectively for 2 yr. Serum PTH levels were unequivocally elevated. The baseline PTH level was 2.8 +/- 1.2 pmol/L and increased progressively to 3.9 +/- 1.5 pmol/L after 2 yr (P < 0.0005). There was no change in serum calcium, alkaline phosphatase, inorganic phosphate concentrations or tubular reabsorption of phosphate in relation to glomerular filtration rate. Fasting urinary reabsorption of calcium increased significantly (P < 0.0005), which was concordant with the PTH change. Fasting and 24-h urinary excretion of calcium decreased significantly (P < 0.0005), suggesting reduced, rather than enhanced, bone resorption as in primary hyperparathyroidism. This may be the main mechanism in maintaining normocalcemia, despite PTH elevation, during lithium therapy.