Temperature regulation in MR-guided focused ultrasound requires rapid MR temperature mapping and automatic feedback control of the ultrasound output. Here, a regulation method is proposed based on a physical model of local energy deposition and heat conduction. The real-time evaluation of local temperature gradients from temperature maps is an essential element of the control system. Each time a new image is available, ultrasound power is adjusted on-the-fly in order to obtain the desired evolution of the focal point temperature. In vitro and in vivo performance indicated fast and accurate control of temperature and a large tolerance of errors in initial estimates of ultrasound absorption and heat conduction. When using correct estimates for the physical parameters of the model, focal point temperature was controlled within the measurement noise limit. Initial errors in absorption and diffusion parameters are compensated for exponentially with a user-defined response time, which is suggested to be on the order of 10 sec.