Rationale: Diesel exhaust (DE), an established model of traffic-related air pollution, contributes significantly to the global burden of asthma and may augment the effects of allergen inhalation. Newer diesel particulate-filtering technologies may increase NO2 emissions, raising questions regarding their effectiveness in reducing harm from associated engine output. Objectives: To assess the effects of diesel exhaust and allergen co-exposure on lung function, airway responsiveness, and circulating leukocytes, and determine whether diesel exhaust particle-depletion remediates these effects. Methods: In this randomized double-blinded crossover study, 14 allergen-sensitized participants (9 with airway hyper-responsiveness) underwent an inhaled allergen challenge after 2h exposures to DE, particle-depleted DE (PDDE) or filtered air. The control condition was inhaled saline after filtered air. Blood sampling and spirometry were performed before and up to 48h after exposures. Airway responsiveness was evaluated at 24h. Measurements and Main Results: PDDE-allergen co-exposure impaired lung function more than DE-allergen, particularly in those genetically at risk. DE-allergen and PDDE-allergen each increased airway-responsiveness in normally-responsive participants. DE-allergen increased blood neutrophils, and was associated with persistent eosinophilia at 48h. DE and PDDE each increased total peripheral leukocyte counts in a manner affected by participant genotypes. Changes in peripheral leukocytes correlated with lung function decline. Conclusions: Co-exposure to diesel exhaust and allergen impaired lung function, which was worse after particle-depletion (which increased NO2). Thus, particulates are not necessarily the sole or main culprit responsible for all harmful effects of diesel exhaust. Policies and technologies aimed at protecting public health should be scrutinized in that regard.