A health hazard to welders is development of lung cancer. It is believed that this is likely due, in part, to the presence in welding fumes of several hexavalent chromium (Cr[VI]) species, whose solubility depends primarily on which process (i.e., manual metal arc verus metal-inert gas) is used. However, inhalation of Cr alone is uncommon in this setting. Thus, an examination of potential contributions from other coinhalants in creating or enhancing conditions whereby inhaled fume-associated Cr (primarily the insoluble forms) may initiate cancer is critical to increasing our understanding and preventing this particular occupational disease. One major chemical species formed and released during welding is ozone (O3). Though implications of adverse pulmonary effects from individual exposure to Cr or O3 have been investigated, those from simultaneous exposure are unclear. To begin to address whether the carcinogenic potential of insoluble Cr[VI] agents might be enhanced in hosts inhaling mixtures of Cr and O3 versus Cr alone, analyses of total lung Cr burden, Cr retention in lung epithelium and interstitium, and potential shifts in lung cell distribution of Cr from the cytoplasm to nuclei were undertaken in F-344 rats exposed nose-only (5 h/d, 5 d/wk for up to 48 wk) to an extrapolated occupationally relevant level of Cr (360 micrograms Cr/m3 as calcium chromate) alone and in combination with 0.3 ppm O3. Overall, there was only a nominal effect from O3 on Cr retention or on distribution of Cr particles among extracellular sites and within lung cells. However, there were O3-related effects upon mechanisms for clearing the Cr from the deep lung, specifically at the levels of particle uptake and postphagocytic/endocytic processing by macrophages. This O3 exposure-related shift in normal pulmonary clearance might potentially increase the health risk in workers exposed to other insoluble or poorly soluble carcinogenic Cr compounds.