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The objectives of this study are to describe and evaluate district-level priority setting, to develop and implement improvement strategies guided by an explicit ethical framework Accountability for Reasonableness (AFR) and to measure their effect on quality, equity and trust indicators within selected disease and programme interventions and services, within general care and on health systems management. Efforts to improve health sector performance have not yet been satisfactory, and adequate and sustainable improvements in health outcomes have not been shown. Priority setting in health systems has mainly been based on the burden of disease approach, cost effectiveness and other evidence-based measures. However, these approaches do not equip decision-makers to address a broader range of values - such as compassion, equity, accountability and transparency - that are of concern to other partners and, not least, the populations concerned. A new focus for priority setting is needed.AFR is a framework for legitimate and fair priority setting that provides decision-makers with an explicit tool for identifying and considering a wide range of relevant values, and defines priority-setting decisions as necessary compromises between partners. AFR makes continued reference to four conditions: relevance to the local setting, decided by agreed criteria; publicizing priority-setting decisions and the reasons behind them; the establishment of revisions/appeal mechanisms for challenging and revising decisions; and the provision of leadership and the enforcement of conditions. REACT - "REsponse to ACcountable priority setting for Trust in health systems" is an EU-funded five-year intervention study, which started in 2006 testing the application and effects of the AFR approach in one district each in Kenya, Tanzania and Zambia. Qualitative and quantitative methods are applied in an action research framework. The project baseline surveys have already been completed and indicate both a strong need and a high willingness for change in the study districts. REACT has developed active research collaborations with an increasing range of actors, including the communities themselves, into a joint research and development process for priority setting for health. The AFR concept and the analysis of the baseline results will be presented and their broad applicability in terms of making sustainable improvements to health systems performance discussed.