AIM To investigate the occupancy at brain 5-hydroxytryptamine (5-HT) 1B receptors in human subjects after administration of the antimigraine drug zolmitriptan. METHODS Positron emission tomography (PET) studies were undertaken using the radioligand [(11)C]AZ10419369 in eight control subjects at baseline and after administration of zolmitriptan orodispersible tablets. The subjects were examined after two consecutive administrations of 10 mg zolmitriptan, approximately 1 week apart. Two of the subjects were subsequently examined after administration of 5 mg zolmitriptan. One week after the last administration of zolmitriptan five of the subjects underwent additional PET measurements without drug pretreatment. RESULTS After administration of 10 mg zolmitriptan, mean receptor occupancy was 4-5%. No consistent changes in 5-HT1B receptor binding were observed for subjects who received 5 mg zolmitriptan. There was a statistically significant negative relationship between binding potential ( BP ND) and plasma concentration of zolmitriptan and the active metabolite 183C91, respectively. All of the five subjects who were examined 1 week after dosing with zolmitriptan showed higher BP ND post drug administration compared with baseline. CONCLUSION This is the first demonstration of CNS 5-HT1B receptor occupancy of a triptan. The findings are consistent with the low receptor occupancy previously reported in PET studies with agonists at other G protein coupled receptors.