This funding opportunity announcement (FOA) invites research projects that seek to explain the underlying mechanisms, processes, and trajectories of social relationships and how these factors affect outcomes in human health, illness, recovery, and overall wellbeing. Types of projects submitted under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical and/or behavioral outcomes in humans to understand fundamental aspects of phenomena related to social connectedness and isolatedness. NIH considers such studies as prospective basic science studies involving human participants that meet the NIH definition of basic research and fall within the NIH definition of clinical trials (see, e.g., NOT-OD-19-024) Types of studies that should submit under this FOA include studies that prospectively assign human participants to conditions (i.e., experimentally manipulate independent variables) and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena without specific application towards processes or products in mind. Applications proposing studies that include but not limited to model animal research or observational studies involving humans should submit under the companion Clinical Trials Not Allowed version of this FOA.