Highly uniform and well-dispersed CaF(2) hollow spheres with tunable particle size (300-930 nm) have been synthesized by a facile hydrothermal process. Their shells are composed of numerous nanocrystals (about 40 nm in diameter). The morphology and size of the CaF(2) products are strongly dependent on experimental parameters such as reaction time, pH value, and organic additives. The size of the CaF(2) hollow spheres can be controlled from 300 to 930 nm by adjusting the pH value. Nitrogen adsorption-desorption measurements suggest that mesopores (av 24.6 nm) exist in these hollow spheres. In addition, Ce(3+)/Tb(3+)-codoped CaF(2) hollow spheres can be prepared similarly, and show efficient energy transfer from Ce(3+) to Tb(3+) and strong green photoluminescence of Tb(3+) (541 nm, (5)D(4)-->(7)F(5) transition of Tb(3+), the highest quantum efficiency reaches 77%). The monodisperse CaF(2):Ce(3+)/Tb(3+) hollow spheres also have desirable properties as drug carriers. Ibuprofen-loaded CaF(2):Ce(3+)/Tb(3+) samples still show green luminescence of Tb(3+) under UV irradiation, and the emission intensity of Tb(3+) in the drug-carrier system varies with the released amount of ibuprofen, so that drug release can be easily tracked and monitored by means of the change in luminescence intensity. The formation mechanism and luminescent and drug-release properties were studied in detail.