The purpose of this funding opportunity announcement (FOA) is to support developmental/exploratory studies in preparation for health promotion, disease prevention, treatment, or treatment services research to improve health in Native American (NA) populations. Applications may include 1) etiologic research, where there is a significant gap in knowledge, that will directly inform intervention development or adaptations, 2) research to develop and pilot test new or adapted interventions for feasibility, acceptability, and scalability, 3) research to test the short-term efficacy of interventions, 4) where a sufficient body of knowledge on intervention efficacy exists, research on strategies to overcome barriers to the adoption, integration, scale-up, and sustainability of effective interventions. Existing data suggest that significant acute and chronic disease inequities exist for NA populations. Concurrently, NA populations experience unique sociopolitical, historical, and environmental stressors and risks that may exacerbate health conditions and/or impact the effectiveness of existing solutions to address the conditions. They also possess unique strengths and resiliencies that can mitigate stressors or inform intervention strategies. Through this announcement, culturally informed exploratory/developmental research is sought that builds upon community knowledge, resources, and resilience to provide foundational knowledge for future science-based, culturally appropriate solutions to reduce morbidity and mortality through identification and remediation of precursors to diseases and disorders and through culturally informed treatment. For the purposes of this FOA, Native Americans include the following populations: Alaska Natives, American Indians (whose ancestral lands fall at least partially within the U.S. mainland border), and Native Hawaiians. The term ‘Native Hawaiian’ means any individual any of whose ancestors were natives, prior to 1778, of the area which now comprises the State of Hawaii.