A device, system, and method for activating and initializing an in vivo imaging device with an RF radiation signal. Functionality of the in vivo imaging device is tested and results may be reported to a user. The in vivo imaging device may include an RF switch to facilitate powering or deactivation of one or more electrical components of the device. The initialization system may include an optical artifact testing unit, a field of illumination testing unit, and a transmission/reception testing unit. The activation system may comprise an in vivo device association unit which may relate a designated device to a single data recorder or to a single controller.