A simple in vitro solubility test for uranium tetrafluoride (UF4) was developed to investigate the effects of addition of enzymes, proteins or gases such as O2 to synthetic biological fluid or Gamble solvent. The tests were conducted concomitantly with an in vivo inhalation experiment using male rats. In the presence of Gamble solvent alone, UF4 exhibited class Y behaviour with a dissolution half-time of 300-500 days. However, when oxygen or carbonates were added to the Gamble solvent, UF4 displayed class W behaviour, with a half-time of 25-50 days. Lastly, in the presence of oxygen and pyrogallol, which simulates the action of the enzyme NADPH, the superoxide ion (O2-) was formed, which appears to have a dominant role in the oxidation of U4+ to U6+. Under these conditions UF4 behaved like a class D compound, and had a dissolution half-time of only 2-3 days. These latter results correlated with those of the inhalation experiment in which the dissolution half-time was calculated to be between 2.5 and 5.2 days. The data are also in agreement with urine monitoring data obtained for workers exposed to UF4 over a 20-year period.