We have studied the effects of ketanserin, a specific 5-HT2 antagonist, and zimelidine, a selective inhibitor of 5-HT re-uptake into central nervous system presynaptic terminals, upon basal and TRH stimulated serum TSH and prolactin levels in euthyroid individuals. Ten normal volunteers were studied (five male and five female), each receiving oral ketanserin and oral zimelidine during respective seven day periods, separated by an interval of at least two weeks. A standard TRH test (200 micrograms i.v.) was carried out before and after each period of drug administration, serum samples being obtained for TSH and prolactin estimation. We were unable to demonstrate any modification of basal or TRH-stimulated TSH and prolactin levels by the oral administration of either ketanserin or zimelidine, suggesting that 5-HT has no significant role in the physiological release of either TSH or prolactin.