In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg versus placebo.This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC_0–12) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC_2–12) during Period 3.251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC₀₋₁₂ in Period 2 versus Period 1 was 0.13 (0.081–0.182; p<0.0001). Least squares mean difference in TNSS Log AUC₂₋₁₂ for fexofenadine HCl versus placebo during Period 3 was −0.24 (−0.425–−0.047; p=0.0148). One fexofenadine HCl-related adverse event was observed.SAR symptoms evoked by ragweed were aggravated by DEP. Fexofenadine HCl 180 mg was effective in relieving pollen-induced, air pollution-aggravated allergic rhinitis symptoms.