We report on frequency multiplication of microwave radiation by propagating space-charge domains in a semiconductor superlattice; the domains were due to a negative differential mobility of miniband electrons. We irradiated an arrangement of two GaAs/AlAs superlattices, mounted in a rectangular waveguide system, with microwave radiation (frequency near 70 GHz) and observed the generation of harmonics; the conversion of radiation power to the third harmonic showed a remarkable efficiency (5%). A theoretical study, based on a drift-diffusion model for the miniband electrons, suggests that the microwave radiation has driven the formation and annihilation of space-charge domains and that the resulting anharmonic current was the source of the frequency-multiplied radiation. Our results indicate that frequency multiplication by space-charge domains in a semiconductor superlattice can be exploited for efficient generation of submillimeter-wave radiation. (C) 2003 American Institute of Physics.