OBJECTIVE: To outline the rationale, objectives and strategies used in a systematically designed research programmme to study specific weight gain-inducing behaviours, their social-psychological as well as environmental determinants, and the effects of interventions aimed at the prevention of weight gain. DESIGN: The evidence for potential behavioural determinants and strategies to prevent weight gain was reviewed, and the methods applied within the Netherlands Research programme weight gain prevention (NHF-NRG) project were described. The project is designed according to the Intervention Mapping protocol. SETTING: The Netherlands. SUBJECTS: The main target groups are (a) adolescents (12-16 y) in secondary school, (b) young adults (20-40 y) at the workplace and (c) recently retired people (55-65 y) at home. INTERVENTIONS: Each intervention includes an individual component, in which computer-tailored information is provided. Additionally, interventions are aimed at changing environmental components. RESULTS: The short-term results of this project can be expected by the beginning of 2005. Guidelines for nationwide weight gain prevention, based on this research programme, will become available in 2007. CONCLUSIONS: Based on the few interventions that were evaluated to date, no robust conclusions can be drawn regarding the effectiveness of obesity prevention. The systematic and multidisciplinary design of the NHF-NRG programme enables the identification of potentially effective methods and strategies for the prevention of weight gain.