The Southern California Environmental Health Sciences Center's theme is Environmental Exposures, Host Factors and Human Disease. The Center has a multidisciplinary team of investigators from Southern California and features several interdisciplinary cornerstones: detailed exposure assessment; cutting-edge study design; and the basic sciences, including physiology, molecular biology, genetics, physics, chemistry, and engineering. The Center emphasizes environmental exposures of public health importance including air pollution, pesticides, ultraviolet and ionizing radiation, and secondhand smoke. The Center is structured to foster cutting-edge environmental health sciences (EHS) research, build research capacity, recruit and develop investigators, and promote interdisciplinary linkage between research and outreach. It is led by a team of highly accomplished investigators who have a record of collaboration and scientific productivity. Four Research Cores (Cancer, Cardio-respiratory Effects, Exposure Assessment, and Study Design) and two Facility Cores (Biostatistics and Integrative Health Sciences) are the primary structural elements. The Center also features a dynamic Community Outreach and Education Core and a robust Career Development Program. During the 14 years of support, the Center has catalyzed research that has filled critical gaps in environmental health science as well as raised new questions that need to be answered. The Center has been instrumental in recruiting new and accomplished investigators to environmental health science. It has nurtured new research ideas, stimulated greater interactions in existing and new multidisciplinary teams, and supported the development of new technologies and state-of-the-art facilities. The Center's research initiatives for the next five years are new approaches for Chemical and Biological-Based Exposure Assessment for Pollutants; Environmental Epigenomics; Environmental Contributions to Obesity; Pathway Approaches to Linking Environment, Genetics and Health; Air Pollution, Neurodevelopment and Neurological Diseases; Global Environmental Health and Climate Change; and Sunlight in Health and Disease. The Center is poised to advance research in these areas by building on its successful approaches in facilitating cutting-edge environmental health science research.