To investigate whether exogenous hypercalcemia influences the release of TSH from the anterior pituitary, 25 microgram TRH were injected iv in six healthy subjects who were pretreated orally with either 10 mg metoclopramide or placebo and infused iv with either calcium or saline. Under normocalcemic conditions, TRH raised the serum TSH level from 1.1 +/- 0.1 to 8.0 +/- 3.3 microU/ml (P less than 0.01). Exogenous hypercalcemia reduced this TSH response to TRH by 37 +/- 11% (P less than 0.02). Although metoclopramide was without effect on basal TSH release in an additional five healthy subjects and also left TRH-stimulated TSH release unaffected under normocalcemic conditions, oral pretreatment with the drug counteracted the inhibitory effect of hypercalcemia and restored a normal TSH response to TRH in hypercalcemic subjects. These results indicate that exogenous hypercalcemia may potentiate dopaminergic TSH inhibition in normal individuals.