Combustion-generated radicals interact forming polynuclear aromatic hydrocarbons (PAHs), including carcinogens. PAHs aggregate into 20-50 nm particles, which extend into branched-chain structures (soots). Many PAHs, including those in soots, fluoresce upon excitation. We have reported that butadiene soot (BDS), generated during combustion of the high volume petrochemical, 1,3-butadiene, serves as a reproducible example of combustion-derived fine and ultrafine particles, with the potential for acute or delayed health effects. Human bronchoepithelial cells (BEAS-2B) display time- and concentration-dependent responses to BDS exposure, culminating in concentration of fluorescent PAHs within discrete cytoplasmic bodies. Here we identify the cytoplasmic compartment(s) in which combustion-derived PAHs concentrate and assess the metabolic responses associated with this compartmentalization. BDS-associated fluorescence co-localized with a red fluorescent cholesterol analog and a transfected plasmid coding for a fluorescent lipid droplet surface protein within BEAS-2B cells. After BDS exposure, murine alveolar macrophages (MH-S) and adipocytes (3T3-L1) also develop fluorescence. These findings, especially within adipocytes, support the accumulation of PAHs within lipid droplets. Microarray data revealed up-regulation of aryl hydrocarbon receptor (AhR)-induced Phase I biotransformation enzymes and nuclear erythroid-2 related factor 2 (NRF2)-mediated oxidative stress responses in BEAS-2B cells. Quantitative RT-PCR results confirmed a time-dependent up-regulation of Phase I biotransformation enzymes (CYP1A1, CYP1B1 and ALDH3A1) in BDS-exposed BEAS-2B and MH-S cells. Thus, respiratory cell lipid droplets concentrate PAHs delivered by combustion-derived ultrafine particles. These PAHs, including several found in BDS and in cigarette smoke, activate xenobiotic metabolism pathways and thereby potentiate their toxicity.