Serum calcium was measured under different circumstances of thyroid dysfunction in male Sprague-Dawley and female Wistar rats. After induction of hypothyroidism with 131I and propylthiouracil, serum calcium fell from a control value of 2.43 +/- 0.08 mmol/l to 2.07 +/- 0.08 mmol/l (P less than 0.01). Thyroid hormone replacement therapy in hypothyroid rats caused a return of serum calcium to control values (2.09 +/- 0.04 mmol/l to 2.41 +/- 0.02 mmol/l, P less than 0.01). Treatment of normal rats with thyroid hormones caused elevation of serum calcium to 2.59 +/- 0.04 mmol/l compared with a control value of 2.44 +/- 0.02 mmol/l (P less than 0.01). Time-course studies demonstrated a slow decline in serum calcium levels over a 10 week period during induction of hypothyroidism with propylthiouracil alone but a very rapid normalization of serum calcium (within 1 h) after replacement therapy with L-tri-iodothyronine. These data illustrate the considerable influence that thyroid hormones exert on calcium metabolism and demonstrate for the first time consistent changes in serum calcium in the rat with hypo- and hyper-thyroidism.