The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry was created by collaboration of the Oklahoma Blood Institute and the Colleges of Medicine and Public Health of the University of Oklahoma Health Sciences Center, combining their respective strengths of community service, patient care, education, and clinical research methodology. The organization of the Registry is based on the fundamental principles of patient-oriented research: 1) all consecutive patients are identified at a uniform time early in the course of their disease; 2) analysis of clinical data requires quantitative and reproducible definitions; 3) patient follow-up is complete; and 4) therefore the data are generalizable to community practice. A summary of 15 years experience with 301 consecutive patients is presented. Some of these results and interpretations are different from other case series. These differences emphasize the distinct perspective of the Registry that includes all patients in the community who have had a clinical diagnosis of TTP or HUS and for whom plasma-exchange treatment was requested. The Oklahoma TTP-HUS Registry provides educational and research opportunities, in addition to improved patient care, and serves as a model for productive collaboration of community blood centers and universities.