This application for support of years 5 to 10 of the Mental Retardation Research Center (MRRC) at the Kennedy Krieger Institute and Johns Hopkins University is submitted in response to RFA HD-93-1. The MRRC includes an Administrative Core that provides general management and biostatistical services, and five research cores. The Genetics Core provides a centralized tissue culture and DNA facility, including an archive of transformed cell lines, specialized cytogenetic analyses, and a genetic data and processing resource. The Neuroscience Core provides quantitative measurements of neurotransmitters and receptors and, when available, their RNA and DNA progenitors, in body fluids and tissue sections, as well as specialized analytical and enzymatic studies of key metabolic intermediates. The Animal Facility Core provides and maintains stocks of genetically unique animals that serve as models for the understanding and therapy of human disease states, and also relates to a transgenic mouse and embryonal stem cell resource. The Neuroimaging Core provides specialized resources for the collection and quantitative analysis of data obtained by positron emission tomography, magnetic resonance imaging and spectroscopy. The Behavior Science Core aids in the design and collection of behavioral data, correlates behavioral and learning deficits with alterations in brain structure and function, and engages in compliance training that includes the preparation of research participants to cooperate with experimental protocols. The core units provide service to 90 investigators in 18 departments who have assembled 52 projects supported by NIH at a total annual direct fundings level of $14,716,280. The program addresses 19 of the 20 priority areas specified in RFA HD-93-1. There is a strong focus on interdisciplinary cooperation, including that between the behavioral and biomedical sciences, and on the prompt testing and utilization of research findings for the benefit of persons who are mentally retarded.