Lung dissolution of industrial uranium tetrafluoride (UF4) was tested in rats and baboons by intratracheal instillation and inhalation, to check the W classification given to UF4 by the International Commission on Radiological Protection. Rats and baboons were given 10 and 160 fJ.g of UF4 per animal respectively. Lung clearance, urinary excretion and tissue distribution of uranium were measured in rats, and urinary excretion was measured in baboons. After intratracheal instillation, daily urinary excretion was fast in both species; 4.8 ± 0.7 x 10-2 of the initial lung burden (ILB) in rats and 2.9 ± 0.3 x 10-2 in baboons. After inhalation of dry UF4 powder, daily urinary excretion was 5.6 ± 2.2 x 10-2 of the ILB in rats and the lung clearance half-life was 7.3 d. The amounts of uranium excreted by rats and baboons were compared to the amounts dissolved in vitro by alveolar macrophages from both species, and also to the amount dissolved chemically by a serum simulant. Both rat and baboon macrophages were clearly shown to be involved in the mechanism of uranium dissolution, since on the first day of macrophage culture, they dissolved 20 and 40% respectively of the amounts of UF4 added to the macrophage cultures, again illustrating the fast dissolution of UF4. Chemical dissolution of the latter with serum simulant was slow, but oxygenation of the simulant raised hourly dissolution fifty-fold and gave a daily uranium excretion rate of 3.4 x 10-2 of the UF4 added to the preparation, which was very close to the urinary excretion rates for both species. The good agreement between the in vivo and in vitro results for both rats and baboons therefore provides evidence that dissolution of UF4 in the lung is fast, and that this compound is more soluble than expected.