Calcitonin determination is of central importance in the diagnosis and follow-up of medullary thyroid carcinoma. Stimulation tests must be applied, particulary for early recognition of familial medullary thyroid carcinomas and for early diagnosis of relapses/metastases, since the basal calcitonin levels are still within the normal range initially. The pentagastrin stimulation test has proven to be the most effective one, though it is associated with considerable adverse effects. TRH is also able to stimulate calcitonin secretion in medullary thyroid carcinoma. The present study examines the value of TRH stimulation compared with pentagastrin stimulation in patients with occult or manifest metastases of medullary thyroid carcinoma. Both patients with occult metastases displayed a marked calcitonin increase after pentagastrin stimulation, but not after TRH stimulation. While calcitonin increased after pentagastrin in the two patients with manifest metastases, TRH produced a clear rise in only one of them and even caused the serum calcitonin concentration to drop continuously in the other one. Thus, TRH cannot be regarded as a reliable calcitonin stimulant in medullary thyroid carcinoma.