The similarity of mode of action, behavior, and gene response between Drosophila melanogaster and mammalian systems, combined with the power of genetics, have recently made the fly an attractive system to study underlying mechanisms of drug abuse, addiction, and mental disorders. The present studies define the behavioral and molecular effects of the powerful hallucinogen lysergic acid diethylamide in Drosophila. Pharmacological activation of serotonin receptors in the fly by lysergic acid diethylamide induces behaviors not unlike those observed in mammalian systems. These include alterations in visual processing abilities, reduced locomotor activity, and altered gene expression within the brain. Many of these effects are due to activation of the same serotonin receptor subtypes that are thought to be the primary mediators of hallucinogenic drug effects in humans as well as the acute symptoms of schizophrenia.We suggest that Drosophila can be used as a genetically tractable model system to define the molecular events leading from serotonin receptor activation to behavior, possibly revealing new targets for hallucinogenic agents and for the treatment of neuropsychiatric disorders such as schizophrenia.