Background: The negative effects of air pollution on morbidity and mortality have been known since the mid 20th century. The two most well known examples are the Meuse Valley disaster in the 1930’ies and the London black fog in December 1952. Whilst there are numerous epidemiological studies, in which associations between morbidity and mortality and high levels of pollutants have been reported, the underlying mechanisms are not clear. Two of the main air pollutants are particulate matter (PM) mostly emanating from diesel exhaust (DE), and ozone, both of which are highly oxidative. Exposure to DE has resulted in adverse effects both in the respiratory tract and in the cardiovascular system. High ozone levels have also been shown to be associated with increased admissions to hospital for respiratory as well as cardiovascular conditions. The main aim of this thesis was to investigate the respiratory and cardiovascular effects of a combination of exposures to ozone and DE. DE generated during the urban part of the standardized European Transient Cycle (ETC) was compared to DE generated by an idling engine. It was also evaluated whether an acute exposure to ozone would have any effects on the cardiovascular system as assessed by venous occlusion forearm plethysmography and heart rate variability (HRV). In addition, fraction of exhaled nitric oxide (FENO) was evaluated as a potential marker for acute exposure to ozone or DE. Methods: Four double-blind randomized cross-over exposure studies were conducted to investigate the effects of ozone and DE on both the respiratory tract and the vascular function in healthy volunteers. All of the exposures were performed in purposely built “walk-in” chambers with strictly controlled exposures. In the first study, the volunteers were exposed to DE (300µg/m3) generated by an idling engine or to air, for one hour in the morning and to ozone (200 ppb) for two hours in the afternoon. A bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 24 hours after the initial exposure. In study II and III, an assessment of vascular function using venous occlusion forearm plethysmography was performed after an exposure to DE (250 µg/m3) generated under transient running conditions, compared to air exposure (study II) and ozone and air exposure (study III). HRV was assessed under a 24 hour period starting before each exposure (study III). In study IV, FENO measurements were conducted after DE and ozone exposures to investigate whether the previously established airway inflammation would be detectable by this non-invasive method. Results: DE exposure enhanced the established ozone-induced airway inflammation in terms of a pronounced neutrophilia in BW. DE generated under transient running conditions, impaired vascular function in healthy volunteers, whereas exposure to ozone did not. HRV were not altered by exposure to ozone. Exposure to DE caused a significant increase in FENO at the 10  (FENO10) and 50 (FENO50) mL/s flow rates at 6 hours post-exposure, but ozone exposure did not affect FENO at any flow rate or time point. Conclusion: We have tried to mimic real-life exposure to air pollutants. In the first study, an exposure to DE followed by an exposure to ozone in the afternoon resulted in an enhanced airway inflammation, suggesting an additive or synergistic effect, supporting the epidemiological findings of unfavorable effects of the combination of these two air pollutants. DE generated by an engine running at the urban part of the standardized European Transient Cycle impaired two important and complementary aspects of vascular function, the regulation of vascular tone and endogenous fibrinolysis. This has previously been shown with DE generated at idling conditions. This suggests that the mechanisms behind the adverse effects can be found in the properties of the particles and not in the gaseous components. In these studies, exposure to ozone did not impair vascular function in healthy subjects, or cause any alterations in HRV. This suggests that the epidemiological evidence for an increased risk of cardiovascular mortality following acute exposure to ozone might not be totally accurate. Previous controlled exposure studies with ozone have not shown an airway inflammation affecting the endothelium, at least not in the same time-frame as following DE exposure. FENO could possibly be a useful tool for assessing airway inflammation caused by DE, whereas the powerful oxidant ozone did not affect FENO. This suggests that the airway inflammatory effects caused by these two pollutants are regulated via different mechanisms.