Objectives: The objective of this paper is to summarize the planning for Phase I of the Marshfield Clinic Personalized Medicine Research Project (PMRP) and to describe the recruitment efforts in the first 2 years. Methods: The purpose of Phase I of the PMRP was to develop a large population-based biobank with DNA, plasma and serum samples to facilitate genomics research. Planning and consultation was facilitated with three external boards: the Ethics and Security Advisory Board; the Scientific Advisory Board; and the Community Advisory Group. Commencing in September 2002, residents aged 18 and above who resided in 1 of 19 zip codes surrounding Marshfield, WI, USA, were invited to participate. After providing written informed consent, participants completed brief questionnaires that included questions about demographics, some environmental exposures, family history of disease, and adverse drug reactions, as well as family members living in the study area. Participants provided 50 ml of blood from which DNA was extracted and plasma and serum samples were stored. The informed consent document allowed access to electronic medical records and included language about non-disclosure of personal research results. A tick-off box was also included so that participants could either allow or decline subsequent recontact for future research studies. Results: A total of 17,463 subjects were enrolled during the first 23 months of recruitment (44.3% of the residents who the Research Project Assistants were able to contact). The participants ranged in age from 18 to 98.5 years (mean = 48.9, median = 48); 57.2% (n = 9986) were female. Self-reported race in the study cohort was similar to the year 2000 census for Wood County, WI, USA, with the majority (98%) reporting themselves to be White Caucasian. The majority of subjects (n = 13,391, 76.7%) indicated that they had German ancestry. Only 142 participants (< 1%) opted out on the consent form for contact for future studies. The majority of the cohort reported that their current area of residence was a suburb, city or village (n = 10630, 60.87%); the remainder reported residence in a rural home or hobby farm (n = 5365, 30.72%), or a working farm or ranch (n = 1451, 8.31%). More than half the cohort (n = 9409, 53.88%) had lived on a working farm at some point in their life. Conclusion: The PMRP database will allow research in three areas: genetic epidemiology, pharmacogenetics, and population genetics. The size and the stability of the population as well as the relative ethnic homogeneity will help facilitate longitudinal studies with valid research results that are not biased by population stratification.