In the last decade, there has been a movement within environmental health and toxicology research to progressively phase out animal testing and implement more rigorous and validated cell culture models. This movement is checked against the rapidly evolving field of immunotoxicology and measurement of immune-mediated cellular responses. Both trends are driven by many variables, some of which are common in both (i.e., increased time constraints; social, financial, and regulatory pressures; and general need to develop modern test bed systems for safety-by-design product development). The need for non-animal alternative test methodology is especially important in the field of immunotoxicology, where increased emphasis has been placed on distinguishing dermal, respiratory, and gastrointestinal sensitization and/or irritation, defining key markers for hazard identification, and developing potential high-throughput screening processes. With these drivers in mind, this article summarizes the key components of developing a prototype test bed system to rapidly determine immunotoxicological responses following exposure to aerosolized materials. Inhalation exposure to aerosolized substances (e.g., chemicals and particles) is a common occurrence for individuals working in research laboratories, engaged in industrial processes, in consumer use of household products, and during the waste disposal process. We recommend research priorities with emphasis on developing continuous flow testing systems, inclusive of aerosolization, cell culture exposure, and immunological endpoint analyses.