BACKGROUND AND AIM[|]Environmental epidemiology has primarily focused on the effects of the outdoor and the built environments, with a secondary interest in the effects of indoor air exposures. Recent events such as climate change and the COVID-19 pandemic have created new awareness and concerns about the effects of the overall indoor environment (where people spend 90 percent of their lives) and the responsibility of expert responses. The complexity of indoor air itself is formidable. Adding the additional variables and complexities of the other primary factors of the indoor environment can quickly overwhelm the structure, methodology, and practicality of environmental epidemiology and associated activities. ASHRAE is a global society with a 130 year history of advancing human well-being through sustainable technology for the built environment. Guideline 10, {Interactions Affecting the Achievement of Acceptable Indoor Environments}, directly addresses the unavoidable complexity by providing a foundational structure within a comprehensible framework for identifying and evaluating the complex interactions of the indoor environment as a whole rather than separately.[¤]METHOD[|]Guideline 10 reflects scientific data known to the ASHRAE committee, or brought to its attention by commenters, as valid and relevant. The Guideline also contains information that represents the professional judgment of the committee members who are deemed to be experts in the field.[¤]RESULTS[|]The foundation of Guideline 10 is the four factors of Thermal, Indoor Air Quality, Sound, and Light (visual). It then identifies the fundamental interactions among and between them in a prioritized structure. Each of the interaction combinations is identified and discussed in the document..[¤]CONCLUSIONS[|]Guideline 10, or similar, is capable of identifying and managing much of the increased complexity of indoor environments acceptable to people. The framework also has the potential for achieving previously disparate goals of environmental responsibilities, ethics, and effective communication between and among the various scientific and public "silos."[¤]