Serotonin is an important modulator of many developmental, behavioral, and physiological processes, and it has been implicated in depression, anxiety, schizophrenia, obsessive compulsive disorders, and substance abuse. Serotonin’s pharmacology is extremely complex and it is mediated by seven of serotonin receptor subtypes and it is present in several tissues. Although it has been a subject of a number of studies, its role has been difficult to ascertain. To investigate the role of serotonin in these disorders, the murine gene was disrupted by homologous recombination. Results indicate that serotonin binding sites were absent in different brain regions (brain stem, frontal cortex, hippocampus, and striatum), and its concentrations were reduced by 60-80%. These mice represent a powerful tool for the investigation of behavioral and neuropsychiatric disorders, and development of drug treatments for these disorders.