This article reports the fabrication of mesoporous Fe(3)O(4) nano/microspheres with a high surface area value (163 m(2)/g, Brunauer-Emmett-Teller) and demonstrates their use for drug loading, release, and magnetic resonance imaging (MRI). These monodispersed, mesoporous Fe(3)O(4) nano/microspheres with controllable average sizes ranging from 50 to 200 nm were synthesized using a Fe(3)O(4)/poly(acrylic acid) hybrid sphere template and subsequent silica shell formation and removal. We found that the SiO(2) coating is a crucial step for the successful synthesis of uniform mesoporous Fe(3)O(4) nano/microspheres. The as-synthesized mesoporous Fe(3)O(4) nanospheres show a high magnetic saturation value (M(s) = 48.6 emu/g) and could be used as MRI contrast agents (r(2) = 36.3 s(-1) mM(-1)). Trypan blue exclusion and MTT assay (see Supporting Information ) cytotoxicity analyses of the nanospheres based on HepG2 and MDCK cells showed that the products were biocompatible, with a lower toxicity than lipofectamine (positive control). Hydrophilic ibuprofen and hydrophobic zinc(II) phthalocyanine drug loading into mesoporous Fe(3)O(4) nanospheres and selected release experiments were successfully achieved. The potential use of mesoporous Fe(3)O(4) nanospheres in biomedical applications, in light of the nano/microspheres' efficient drug loading and release, MRI, and low cytotoxicity, has been demonstrated. It is envisaged that mesoporous Fe(3)O(4) nanospheres can be used as drug carriers and MRI contrast agents for the reticuloendothelial system; they can also be delivered locally, such as via a selective catheter.