This study presents different research techniques linked together to improve our understanding of the particulate matter (PM) impacts on health. PM samples from the exhaust of different vehicles were collected by a versatile aerosol concentration enrichment system (VACES). Waterborne PM samples were collected with this technique, thus retaining the original physicochemical characteristics of aerosol particles. PM samples originated from a gasoline Euro 3 car and two diesel cars complying with the Euro 2 and Euro 4 standards, respectively. The Euro 2 diesel car operated consecutively on fossil diesel and biodiesel. The Euro 4 car was also retrofitted with a diesel particle filter. In total, five vehicle configurations and an equal number of samples were examined. Each sample was intratracheally instilled to 10 mice at two different dose levels (50 and 100 μL). The mice were analyzed 24 h after instillation for acute lung inflammation by bronchoalveolar lavage and also for hematological changes. Results show that a moderate but still significant inflammatory response is induced by PM samples, depending on the vehicle. Several organic and inorganic species, including benz(a)anthracene, chrysene, Mn, Fe, Cu, and heavy polycyclic aromatic hydrocarbons (PAHs), as well as the reactive oxygen species content of the PM suspensions are correlated to the observed responses. The study develops conceptual dose-response functions for the different vehicle configurations. These demonstrate that inflammatory response is not directly proportional to the mass dose level of the administered PM and that the relative toxicity potency depends on the dosage level.