This study investigates the relationship between the size, composition, and biological effects of coarse (2.5–10 μm), fine (< 2.5 μm), and ultrafine (< 0.1 μm) particulate matter (PM) on macrophages and epithelial cells. The research focuses on the induction of oxidative stress and mitochondrial damage. Ultrafine particles (UFPs) were found to be more potent in inducing heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione, which are markers of oxidative stress. The DTT assay, a quantitative measure of in vitro reactive oxygen species (ROS) formation, was correlated with PAH content and HO-1 expression, with UFPs showing the highest ROS activity. Electron microscopy revealed that UFPs and fine particles localized in mitochondria, causing significant structural damage. The study concludes that the increased biological potency of UFPs is related to their content of redox cycling organic chemicals and their ability to damage mitochondria, contributing to their adverse health effects.This study investigates the relationship between the size, composition, and biological effects of coarse (2.5–10 μm), fine (< 2.5 μm), and ultrafine (< 0.1 μm) particulate matter (PM) on macrophages and epithelial cells. The research focuses on the induction of oxidative stress and mitochondrial damage. Ultrafine particles (UFPs) were found to be more potent in inducing heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione, which are markers of oxidative stress. The DTT assay, a quantitative measure of in vitro reactive oxygen species (ROS) formation, was correlated with PAH content and HO-1 expression, with UFPs showing the highest ROS activity. Electron microscopy revealed that UFPs and fine particles localized in mitochondria, causing significant structural damage. The study concludes that the increased biological potency of UFPs is related to their content of redox cycling organic chemicals and their ability to damage mitochondria, contributing to their adverse health effects.