The lung retention of uranium was determined in rats that inhaled aerosols of commercial yellowcake powders obtained from two mills (Mill A and Mill D) and whose chemical composition and solubilities in vitro were significantly different. Analysis by IR absorption indicated Mill A yellowcake contained 82% ammonium diuranate (ADU) and 18% U3O8. The Mill D powder contained 25% ADU and 75% U3O8. In vitro dissolution studies indicated for the Mill A sample, approximately 85% of the uranium had a dissolution half-time (T 1/2) of less than one day, with the remainder dissolving with a half-time of 500 days. For the Mill D sample, 25% had T 1/2 less than one day and 75% had T 1/2 of 300 days. Groups of 50 rats were exposed by nose-only inhalation to aerosols of either the Mill A or the Mill D yellowcake. Rats were sacrificed in groups of five at intervals through six months after exposure. Selected tissues and excreta samples were assayed by fluorometry to determine their uranium contents. For the Mill A yellowcake, 78% initial lung (broncho-alveolar) burden cleared with T 1/2 of 0.5 days, and 22% with T 1/2 of 240 days. For the Mill D yellowcake, 25% initial lung burden cleared with T 1/2 of 3.5 days and 75% with T 1/2 of 110 days. Thus, the lung clearance of uranium in the rat mimicked the in vitro dissolution data and supported the contention that ADU should be considered as a Class D compound (T 1/2 = 0.5 days) and U3O8 behaves in the lung as a Class Y (T 1/2 greater than 100 days) material.