The invention provides methods for the production of radioisotopes or for the treatment of nuclear waste. In methods of the invention, a solution of heavy water and target material including fissile material present in subcritical amounts is provided in a shielded irradiation vessel. Bremsstrahlung photons are introduced into the solution, and have an energy sufficient to generate photoneutrons by interacting with the nucleus of the deuterons present in the heavy water and the resulting photoneutrons in turn cause fission of the fissile material. The bremsstrahlung photons can be generated with an electron beam and an x-ray converter. Devices of the invention can be small and generate radioisotopes on site, such as at medical facilities and industrial facilities. Solution can be recycled for continued use after recovery of products.