Mesoporous silica nanoparticles (MSNs) containing a hexagonal array of one-dimensional channels with diameters of 2.4 nm were synthesized using a surfactant-templated, base-catalyzed condensation reaction. After extraction of the template, the highly porous 75 nm nanospheres were coated with a Gd-Si-DTTA complex to give MSN-Gd particles that exhibit very high MR relaxivities. The MSN-Gd nanoparticles were characterized using SEM, TEM, TGA, BET, PXRD, and DCP, and the relaxivities were determined on both a 3.0 T and a 9.4 T MR scanner. The MSN-Gd particles exhibit very high MR relaxivity on a per Gd basis and even more impressive MR relaxivity on a per nanoparticle basis, owing to the ready access of water molecules through the nanochannels of the MSN-Gd particles and a high payload of Gd centers. The in vivo efficacy of these particles as MR contrast agents was further demonstrated with monocyte cells and mouse models. Both T1-weighted and T2-weighted signal enhancement can be obtained at doses much lower than what is currently being used. In vitro MTS assay and in vivo mouse studies indicated no acute toxicity of the MSN-Gd nanoparticles. This work thus demonstrates the design and synthesis of highly efficient nanoparticulate MRI contrast agents based on MSNs and suggests the potential of using these new hybrid nanomaterials for early disease diagnosis.