The GCRC at San Francisco General Hospital (SFGH) is now in its 35th year of continuous funding, This renewal application comes three years after the unit moved from an isolated building to the main hospital facility, stimulating considerable interest in the use of the GCRC by a diverse group of investigators who wish to study patients at a high acuity level than we previously possible. Last year we added a separate outpatient clinic to accommodate a rapidly expanding number of protocols that require such a facility. A total of 36 PIs, representing 9 departments, have submitted 68 protocols. Our program is highly diverse, ranging from classic metabolic studies to pharmacokinetics, controlled drug infusions, and a variety of therapeutic trials. As befits a program located at SFGH, AIDS is well represented with am emphasis on pathophysiological mechanisms as well as therapeutics. Examples of studies proposed in this application include: effects of viral infection and multi-day exposure to zone in asthma; fluoxetine and cue-reactivity in amphetamine users; effects of carbon monoxide on the cardiovascular system; clinical pharmacology of nicotine; pathogenesis of low HDL levels in Turks; HIV vaccine trial in healthy adults; salvage therapy for multi-drug resistent TB; gene expression in G protein receptor signaling; HIV-1 protease genotypic resistance patterns; zinc, glucocorticoids and immune function in ESRD; hedgehog signaling pathway in cancers; utilization of health services in Latino women and infants; lymphocyte depletion following HIV infection: malabsorption and energy deficit in AIDS wasting: effect of hypertriglyceridemia on endotoxemia; effectiveness of protease inhibitors in practice; LDL subclass patterns and high carbohydrate diet; hepatic metabolic pathways in NIDDM; metabolic effects of alcohol ingestion; kinetics of circulating HIV and CD4+ cells; de novo nephropathy; markers of acute lung injury in trauma patients; the role of the thymus in HIV disease; viral burden, altered metabolism, and HIV wasting; anabolic and anti-cytokine therapies and their metabolic effects in AIDS; anabolic therapy, amelioration of acidosis and resistance exercise in ESRD; mitigation of episodic wasting in HIV infection. Included in this proposal are expanded activities for and plans to renovate the core laboratory and a new initiative to expand training capabilities in patient-oriented research.