The MHCRC on Regional Brain Function in Schizophrenia is dedicated to the multidisciplinary examination of the neurobiology of behavior and aberrations associated with schizophrenia. Our aim is to elucidate mechanisms and principles linking brain systems to behavioral dimensions from the molecular to the clinical level. In such tranlational research it is necessary to combine advanced methodology across a range of expertise in basic and clinical neurosciences with a focus around a set of complementary research strategies aimed at well formulated guiding hypotheses and themes. The MHCRC provides the infrastructure, support an intellectual environment essential for such integrative research through the following Cores. The Infrastructure Cores are Administration; Clinical; Data. The Core Laboratories are Neuropsychology; Structural Imaging; Functional Imaging; Psychophysiology; Image Processing; Genetics and Neurodevelopment; Molecular Neuropathology. The Center capitalizes on the rich resources at the University of Pennsylvania for conducting this challenging research. During the present period of support, this has resulted in a productive and dynamic research enterprise that strives for excellence and has sustained a high level of peer reviewed grant support and publicaitons. In addition to advancing its scientific agenda, the Center has become an educational resource for faculty, fellows, residents and students at all levels. It has also become a clinical resource for individuals with schizophrenia, their families and care providers. The findings across Cores consistently support the notion that has motivated the Center, since its inception in 1988, which considers schizophrenia as a brain disease. By carrying this notion to its conclusion, through application of advanced methods, we have identified abnormalities that suggest neurobiological substrates for this devastating disorder. The results underscore the need to expand the work in the following domains: neurodevelopment and aging, sex differences, vulnerability, specificity and boundaries. These themes will be pursed in the next phase and we believe that with their further elucidation we will be poised to impact the theory and practice in the area of schizophrenia. In particular, the links we are continuously forging between neural and behavioral measures will assure that findings will have implication for treatment and rehabilitation.