An in vitro system for rapidly determining the relative solubilities of plutonium-containing aerosols produced at various temperatures has been developed. Aerosols were prepared by nebulizing a solution of Pu IV in 1M HCl and by subsequent heating at 50, 325, 600, 900, 1150 and 1300°C. These aerosols were then evaluated as to relative solubility and the results compared with in vivo data from beagle dogs and Chinese hamsters. Aerosol samples from animal inhalation exposures were collected on filters and a section was sandwiched between 100 nm membranes held in a two-piece, cylindrical, polyethylene holder. The holder and filter were placed in a container of solvent and stirred gently, after which the filter and solvent were separately analyzed for Pu. The effects of solvent composition, volume and temperature as well as immersion time were investigated. The results showed that using a solvent of 0.1N HCl at 23°C and an immersion time of 2 hr dissolved a sufficient amount of plutonium as to be easily assayed with a liquid scintillation counter and will provide a rapid estimate of the solubility rate of the aerosol. The in vivo and in vitro results were in relative agreement; as the production temperature of the aerosol increased, the solubility decreased.