To test the hypothesis that PRL is able to feedback negatively on its own secretion (short-loop feedback) in humans via augmentation of the turnover of tuberoinfundibular dopamine (TIDA), the effects of the administration of purified hPRL on endogenous LH, FSH and TSH were assessed. Purified hPRL, given in an i.v. loading dose of 90 micrograms followed by a continuous infusion of 1.39 micrograms/min to 4 normal male volunteers resulted in a tripling of PRL levels (10.5 +/- 1.9 micrograms/L increasing to 30.9 +/- 3.6 micrograms/L) at the end of 90 min. There were no changes in LH, FSH or TSH levels, however, during or following the infusion. Purified hPRL was also given in 1 and 8 micrograms/kg doses IM to 5 normal male volunteers. Although PRL levels did not rise significantly with the 1 microgram/kg dose, levels almost doubled with the 8 micrograms/kg dose (9.5 +/- 2.2 micrograms/L increasing to 17.4 +/- 1.5 micrograms/L). Again, LH, FSH and TSH levels did not change significantly over the three hour period of sampling with either dose. In conclusion, in this study we found that a 2-3 fold increase of circulating PRL levels maintained for 1.5-3 h exerted no apparent effects on the secretion of endogenous LH, FSH and TSH. This study provides direct evidence against the existence of a short-loop feedback occurring via TIDA activation in humans over this time interval but does not rule out the possibility that such feedback may occur with more prolonged states of hyperprolactinemia or via other mechanisms or the possibility of an effect on the hypothalamic pulse generator.