Research problems in human biology, clinical medicine, and health services delivery are complex, and increasingly require collaborative approaches. Despite the commitment of general internists, general pediatricians, and family physicians to comprehensive, coordinated, and longitudinal care, their substantial overlap in research topics, methods, and data sources, and their shared emphasis on research conducted in community-based settings, the three primary care disciplines rarely collaborate in research. The research enterprises of most primary care departments and divisions in the United States are small "cottage industries," while interdepartmental research units are rare. Interdepartmental research units can develop and maintain the critical mass of investigators, trainees, and staff that is necessary for an intellectually vibrant and financially sound primary care research enterprise. The University of Colorado Health Sciences Center School of Medicine has developed a successful interdepartmental research effort in primary care that includes joint fellowship training and faculty development programs and a Primary Care Research Unit that supports the analysis of secondary databases, practice-based research networks, and interdisciplinary research projects. Key elements of this collaboration include shared projects among faculty and trainees, proactive negotiation about resources, and shared research space, staff, and faculty. Such a collaboration provides the breadth of perspectives necessary to address complex health care problems, and the pragmatic infrastructure necessary to sustain research themes and careers.