Understanding the diverse functions of serotonin in the human brain can be obtained through examination of subjects having a lower than normal number of brain serotonin neurons. Behavioral abnormalities consistent with brain serotonergic damage have been reported in some polydrug users who also use the neurotoxin ecstasy (methylenedioxymethamphetamine, MDMA). This review evaluates the evidence from neuroimaging studies that brain serotonergic damage is a feature of human users of ecstasy. To date, neuroimaging studies designed to establish whether levels of brain serotonin neurons are lower than normal in ecstasy users have employed radioligands that bind to one component of the serotonin neuron, the serotonin transporter (SERT). Because these studies are methodologically flawed in terms of reliability or validity of the SERT measurement and appear to have employed polydrug users, no definitive information is yet available on the question of ecstasy toxicity to human brain serotonin neurons. Until these issues are resolved, it cannot be assumed that ecstasy exposure represents a chronic serotonin deficiency condition.