Pharmacological challenge tests provide a method of assessing the functional responsiveness of serotonin (5-HT) receptor subtypes in the human brain. A number of selective agonist ligands for the 5-HT1B/1D receptor are available for human use; however, these compounds do not distinguish between 5-HT1B and 5-HT1D receptors, which is somewhat of a disadvantage. Acute administration of sumatriptan, rizatriptan, and zolmitriptan all increase plasma growth hormone in healthy subjects, possibly via activation of postsynaptic 5-HT1D receptors. This response is blunted in major depression. Sumatriptan lowers plasma prolactin, perhaps via activation of presynaptic 5-HT1B receptors. This response is not altered during repeated treatment with selective serotonin reuptake inhibitors (SSRIs), suggesting that 5-HT1B receptors retain the ability to restrain 5-HT outflow during short-term SSRI treatment.