The National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Heart, Lung and Blood Institute (NHLBI), the National Institute of Neurological Disorders and Stroke (NINDS), and the Office of Research on Women’s Health (ORWH) of the National Institutes of Health (NIH) invite investigator-initiated research applications for mechanistic studies in clinical trials of immunomodulatory interventions for immune system mediated diseases, including, but not limited to, asthma and allergy, graft failure in solid organ, tissue, cell and stem cell transplantation, and autoimmune diseases. Specifically, this Request for Applications (RFA) is a continuation and modification of RFA AI-98-006. It focuses on the inclusion of patients and utilization of patient samples for the evaluation of immunologic and other relevant parameters to facilitate the study and definition of immunological mechanisms underlying the intervention, the mechanisms of disease pathogenesis, surrogate/biomarkers markers of disease activity and therapeutic effect, and mechanisms of human immunologic function. The parent or core clinical trial must have independent financial support and will NOT receive support under this RFA. Proposed mechanistic studies associated with clinical trials supported by industry are particularly encouraged but clinical trials supported by any source, public or private, are eligible.