MRI-guided focused-ultrasound is a non-invasive technique that can enhance the delivery of therapeutic agents. The objective of this work was to develop a focused-ultrasound system for preclinical research in small animals that is capable of sonicating with high spatial precision within a closed-bore MRI. The system features a computer-controlled, non-magnetic, three-axis positioning system that uses piezoelectric actuators and linear optical encoders to position a focused-ultrasound transducer to targeted tissues under MRI guidance. The actuator and encoder signals are transmitted through low-pass-filtered connectors on a grounded RF-penetration panel to prevent artifacts during image acquisition. The transducer is attached to the positioning system by a rigid arm and is submerged within a closed water tank. The arm passes into the tank through flexible bellows to ensure that the system remains sealed. An RF coil acquires high-resolution images in the vicinity of the target tissue. An aperture on the water tank, centered about the RF coil, provides an access point for target sonication. Registration between ultrasound and MRI coordinates involves sonicating a temperature-sensitive phantom and measuring the centroid of the thermal focal zone in 3D with MR thermometry. Linear distances of 5 cm with a positioning resolution of 0.05 mm can be achieved for each axis. The system was operated successfully on MRI scanners from different vendors at both 1.5 and 3.0 T, and simultaneous motion and imaging was possible without any mutual interference or imaging artifacts. This system is used for high-throughput small-animal experiments to study the efficacy of ultrasound-enhanced drug delivery.