A system and method for determining location and orientation of an in-vivo device, with respect to an external system in which the device is located include a frame with external magnets attached thereon. An in-vivo device is inserted into the patients body, which is placed within the system, and the external magnets apply magnetic forces on the in-vivo device. A radio beacon transmitter is attached to the frame for transmitting a radio pulse. The in-vivo device includes an ultrasonic transmitter for transmitting an ultrasonic signal, which is triggered by the radio pulse. At least three transponders are placed on the patients body, each transponder sending a first acoustic signal triggered by the radio pulse, and each sending a second acoustic signal triggered by the devices ultrasonic signal. At least three sonic detectors are located on the frame for detecting each of the transponders first and second sonic signals, and a processor measures time of detection of the transponders signals and thus calculates location of the device in frame coordinates, and in body coordinates.
