DescriptionIntroduction: Diesel exhaust is ubiquitous and has been shown to cause a variety of health effects related to innate immune response in the airways that leads to a cascade of local and systemic health effects. Sex is known to influence variations in immune responses and many other aspects of the internal physiological environment. Aims: The primary aim of this dissertation research is to evaluate whether there are sex differences in the symptomatic, local and systemic inflammation and acute-phase responses that have been attributed to acute diesel exhaust exposure. The secondary aim is to see if sex differences exist in the rates of metabolism of diesel exhaust and its metabolites. Methods: In a crossover design study, healthy subjects were exposed to 300μg/m3 of diesel exhaust and clean air for 1 hour each in a controlled environmental exposure chamber on two different days (≥1 week washout) in random order. Nasal lavage and sputum samples were collected and analyzed for cytokines and soluble proteins in relation to local inflammation. Blood samples were collected and analyzed for cytokines, acute phase reaction proteins, neutrophils and cell blood counts in relation to systemic inflammation. Questionnaires were used to collect self-reported symptoms. Spot urine samples were collected within 24 hours of exposure to analyze the levels of 1-aminopyrene a metabolite of 1-nitropyrene which is the most abundant nitro-polycyclic aromatic hydrocarbons in diesel exhaust. Results: There was a statistically significant sex difference in self reported somatic and lower respiratory symptom severity ratings with females having higher symptom severity ratings than males after exposure to diesel exhaust relative to clean air. There was also a statistically significant sex difference in the concentration of tumor necrosis factor – α in nasal lavage samples and platelet count in peripheral blood with males having higher tumor necrosis factor – α concentrations than females and lower platelet counts than females after exposure to diesel exhaust relative to clean air. Conclusion: Sex is a significant effect modifier for certain health effects of acute diesel exhaust exposure, with females tending to show greater lower respiratory and systemic effects and males tending to show greater upper respiratory effects.