Schizophrenia and related psychoses are chronic brain disorders whose prognosis is often poor and whose pathophysiology remains obscure. Neuroimaging technologies such as PET (positron emission tomography), fMRI (functional magnetic resonance imaging), DTI (diffusion tensor imaging) and MRSI (magnetic resonance spectroscopic imaging) offer opportunities to elucidate the pathophysiology by studying brain function in living patients. The use of these techniques to study psychotic disorders is severely limited, however, by a critical methodological confound: neuroleptic treatment. The purpose of this protocol is to admit patients with schizophrenia and other related disorders to the Clinical Center, carefully evaluate their neuropsychiatric status, and discontinue psychotropic medications for a brief period so patients can be studied without the confound of neuroleptic treatment. There are several phases to this protocol. The first phase is the evaluation phase and includes gathering historical data, structured diagnostic interviews, general physical and laboratory assessments, basic physiological monitoring, neuropsychological testing, limited collection of blood and urine samples, and serial behavioral ratings. In the second phase, patients will receive blinded compounds that will contain inactive placebo or active neuroleptic administered in a double blind, crossover fashion. Each arm normally lasts 4 to 6 weeks. The total duration of this phase is 8 to 12 weeks. During the coded neuroleptic period, patients are enrolled in a series of neuroimaging and other approved protocols designed to elucidate the neurobiology of these disorders. These include studies using PET, fMRI, DTI, and MRSI. The neuroleptic free period is essential to distinguish the effects of illness versus medication. Parameters under investigation include traits that are candidate phenotypes for genetic studies and state-dependent aspects of brain function. The combined use of many neuroimaging modalities will allow us to look at the functional relationship between a variety of brain abnormalities hypothesized to play a role in schizophrenia. These include hippocampal neurochemical abnormalities, deficits in prefrontal cortical activation, and dysregulation of subcortical dopamine in a single patient.