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Rationale Vehicle interiors are an important microenvironment for atopic subjects. This study evaluated the subjective and objective physiologic and clinical effects of exposing subjects with asthma and allergic rhinitis to new 2017 Mercedes vehicles during 90-minute rides. Methods Ten adult asthmatics with allergic rhinitis were assessed before and 45 and 90 minutes into rides in a 2017 Mercedes-Benz S-Class sedan and GLE-Class SUV on 2 separate days. Assessments included spirometry, fractional exhaled nitric oxide, peak nasal inspiratory flow, asthma symptom scores, and physical examinations. Results Of the 10 subjects, 6 were women, mean age was 32 years, and 6 and 4 were using chronic asthma controllers or intranasal corticosteroids, respectively. None of the subjects had worsening of asthma or rhinitis symptoms during the rides. There were no statistically significant changes from baseline in forced expiratory volume in 1 second, forced expiratory volume in 1 second:forced vital capacity ratio, forced expiratory flow at 25%–75% of vital capacity, fractional exhaled nitric oxide, or peak nasal inspiratory flow at 45 or 90 minutes into the rides with either Mercedes vehicle (all P values > .1 using generalized linear mixed model). Conclusion The interior environment of the tested Mercedes vehicles did not cause changes in subjective or objective measures of asthma and allergic rhinitis. We suggest that this model system can be used to test other vehicles for putatively adverse effects on patients with allergic respiratory disorders.