(+/-)3,4-Methylenedioxymethamphetamine (MDMA), a synthetic amphetamine derivative used recreationally by humans, damages brain serotonin neurons in experimental animals. In preclinical studies, serotonin reuptake inhibitors block MDMA-induced serotonin release; they also block MDMA neurotoxicity. Whether serotonin reuptake inhibitors also block MDMA's psychoactive effects in humans has not been established. Reported herein are four individuals who describe their experiences after ingesting fluoxetine, a potent and selective serotonin reuptake inhibitor, before MDMA ingestion. Their reports indicate that fluoxetine does not block MDMA's reinforcing subjective effects and raise the possibility that MDMA's psychoactive effects may be separable from its neurotoxic actions.