Earlier injection and inhalation studies with uranium trioxide (UO3) indicated that the material was more similar to soluble uranyl salts than to the so-called insoluble oxides, U3O8 and UO3, but quantitative data were lacking. This inhalation study of U03 (enriched with 235U) in dogs substantiated the earlier studies with the findings that (a) U03 is rapidly removed from the lungs, with most following a 4.7 day biological half time; (b) systemic absorption amounted to more than 20% of the exposure burden; and (c) more than 20% of the excreted uranium was found in the urine. External measurement of the U03 levels in the lungs (186 keV gamma} produced an erroneous picture of U03 clearance because of appreciable 235U accretion in the extrapulmonary structures of the thorax. The inhalation study was complemented by aerosol and in vitro solubility analyses in order to examine a recently-proposed solubility model for alveolar clearance. The health physics implications of the results are discussed.