Purpose. The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are cooperating to facilitate biomedical research in space for better understanding of human physiology and human health on Earth. The NIH uses this FOA to publicize the availability of the International Space Station (ISS) as a National Laboratory, and to announce the NIH BioMed-ISS program encouraging investigator-initiated applications for biomedical research that will use the unique microgravity and radiation environment and resources of the ISS to test innovative hypotheses for the potential benefit of human health on Earth. Applications to this FOA should propose innovative biomedical research on the molecular or cellular level that is directly relevant to the NIH mission and can be carried out on the ISS. Awards made through this FOA will initially support milestone-driven, ground based preparatory studies (UH2 ground feasibility phase), with possible rapid transition to the second, ISS-based research phase (UH3 ISS experimental phase). The ground feasibility phase (UH2) will allow investigators to focus on ground-based preparatory work to meet scientific milestones and technical requirements leading to the ISS experimental phase (UH3). The UH3 phase will include preparing the experiments for launch, conducting them on the ISS, and the subsequent data analyses on Earth. UH3s will be awarded after administrative review of the eligible UH2s that have met the scientific milestones and feasibility requirements necessary to conduct research on the ISS. The UH2/UH3 application must be submitted as a single application, and applicants should note specific instructions for each phase in this FOA. Mechanism of Support. This BioMed-ISS FOA uses the NIH two-phased Exploratory/Developmental (UH2/UH3) cooperative agreement mechanism. Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of meritorious applications.