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and communication, and permits the integration of primary providers and their practice populations into the clinical research enterprise in ways that were never possible before. The electronic infrastructure for the electronic Primary Care Research Network (ePCRN), a new pilot study funded by the National Institutes of Health Roadmap Initiative ‘Re-engineering the Clinical Research Enterprise’ will take advantage of these recent changes to substantially enhance the potential for the performance of clinical and translational research in primary care. The ePCRN is providing a new model for clinical research in primary care led by the Federation of Practice-based Research Networks, representing over 6500 primary care physicians in the United States performing research in practices primarily committed to patient care, with the advanced Internet-2/Grid technologic infrastructure of the University of Minnesota, the University of California San Francisco (UCSF), and with the web-based primary care RCT support experience of the Midlands Research Practices Consortium (MidReC) in the UK and the American Academy of Family Physicians (AAFP). The ePCRN’s sophisticated electronic support is being developed on the new open grid source architecture–data access and integration (OGSA-DAI) platform for very high-speed network communication. Involving over 100 clinics across the United States, this large NIH project is introducing to the clinics a standardized ‘gateway’ that uses the ASTM medical communication standard the Continuity of Care Record (CCR). Having recently completed its first clinical trial with 100 physicians in <6 weeks, the technology of the ePCRN offers to help fulfill the promise of Practice-based Research Networks to provide for large, fast clinical effectiveness trials in primary care. Some of the capabilities promised by the ePCRN include patient eligibility searches across wide geographic areas, virtual clinical trials, real-time video conferencing, remote instrumentation and the establishment of standardized linkages between primary care clinics. The development of a high-speed electronic research network on open-source Internet-2/Grid functionality that allows primary care clinics to participate as peers in clinical research may be a harbinger of a revolution in clinical and translational research and in primary care in the United States.