Dr. St.Clair, an academic rheumatologist, is strongly committed to a career in patient-oriented research. His clinical research program has focused on the pathogenesis and treatment of rheumatoid arthritis (RA). It has been highly productive within an integrative environment of outstanding clinical investigators, biostatisticians, and basic scientists. A Midcareer Investigator Award would enable Dr. St.Clair to obtain sufficient protected time to expand his successful clinical research program, seize new research opportunities, and build an effective mentoring system that would create a lasting enterprise for future investigators at Duke. Dr. St.Clair has been an active and independent clinical investigator. His current research has centered in part on the role of nitric oxide (NO) as a mediator of joint inflammation. These studies have been performed in collaboration with Dr. J. Brice Weinberg and supported by the Specialized Center for Research in RA. It is funded by the National Institutes of Health (NIH) and continues to yield a wealth of new research ideas and clinical projects. Dr. St.Clair and his coworkers have also just completed an NIH-funded pilot clinical trial of intravenous (i.v.) doxycycline therapy in RA. These data are currently being analyzed and will determine if this i.v. antibiotic regimen has potential clinical benefits in RA and will elucidate possible mechanisms of action. In addition, Dr. St.Clair has been an investigator in several multicenter clinical trials of novel biologics in RA, such as IL-10 and a chimeric anti-tumor necrosis factor-alpha monoclonal antibody, and shown how patient specimens from these trials can be utilized to gain further insights into the biologic effects of cytokine manipulation. Duke University has built an enriching educational environment where Dr. St.Clair can establish an outstanding mentoring program. The centerpiece of the institutional environment is the Clinical Research Training Program. Other resources available to Dr. St.Clair and his trainees include the Department of Medicine Biostatistics Unit, the Duke Clinical Research Institute, and the Center for Health Services Research in Primary Care. The combined talents of many successful investigators at Duke and the availability of these critical resources provide Dr. St.Clair with outstanding clinical research opportunities and educational experiences for his trainees.