The Johns Hopkins General Clinical Research Center (GCRC) on Osler 5 is an institutional resource whose aim is to promote patient oriented research and training on a wide variety of diseases, by a number of clinical investigators from throughout the institution. The Johns Hopkins University School of Medicine has a strong base of externally funded research and training, with many faculty, fellows, housestaff and students. Widespread institutional associations serve as resources for clinical investigation. The GCRC itself is a well equipped, modern, in-patient facility housed in the midst of patient care and clinical training activities. Programs that support training on the GCRC include the institutional clinical scientist awards and a new grad program in clinical research. In 1992, a Supplement to upgrade the computer system and a Clinical Associate Physician proposal were each reviewed and approved with high priority. Over 120 investigators from 17 departments propose to accomplish the 53 protocols described in this application. Each protocol receives internal review of scientific and human subjects considerations, with special attention to gender and ethnic inclusiveness. Areas of scientific emphasis include the development of implanted insulin pump therapy for diabetes, anti-AIDS drug development, anti-cancer drugs, the treatment of adrenoleukodystrophy, and a new treatment of sickle cell anemia. Special emphasis for the next grant period will include the above plus application of new imaging, pet and mass spectroscopy techniques to brain cancer, schizophrenia, and drug abuse, the use of stable isotope techniques to study amino acid metabolism in aging and obesity, and a novel approach to anti-cancer therapy be gene modification. As the infrastructure for adult, in-patient clinical research, this proposal seeks continuation of 2,200 research patient days/year, the research nursing staff, the staffed and equipped research kitchen, the biostatistician, computerized data management and analysis system with system manager, clinical associate physician, program direction and administration. In the broadest sense, the proposal requests support for continuation of a scientifically strong, highly active and efficient GCRC.