NaKo Physical Activity (NaKoPA) is a Competence Unit on Physical Activity of The German National Cohort (GNC), a joint interdisciplinary endeavor which is being implemented by a national network of 25 German research institutions. Its overall aim is to investigate the causes underlying major chronicdiseases, i.e. cardiovascular diseases, cancer, diabetes, neurodegenerative/-psychiatric diseases, respiratory and infectious diseases, and their pre-clinical stages or functional health impairments. In each of 18 study centers, spread across Germany, a random population sample of 100,000 women and 100,000 men aged 20-69 years is being drawn for a broad range of baseline examinations. These include an interview and self-completion questionnaires, several medical examinations and the collection of biological material (blood, urine, saliva, nasal swabs and stool). In a random by selected subgroup of 20 % of the participants (n = 40,000) an intensified examination („Level 2“) program is being performed. In addition, in five of the 18 study centres a total of 30,000 study participants will be examined by magnetic resonance imaging (MRI). These participants will also be offered the intensified Level 2 examinations. All participants will be invited for a re-assessment after 4 years. Information about chronic disease endpoints will be collected through a combination of active follow-up (including questionnaires every 2-3 years) and record linkage. The GNC is planned for an overall duration of 25-30 years. It will provide a major, central resource for population-based epidemiology in Germany, and will help to develop novel strategies for early detection, prediction, and primary prevention of major diseases.