A system and method for radioisotope production uses fast-neutron-caused fission of depleted or naturally occurring uranium targets in an irradiation chamber. Fast fission can be enhanced by having neutrons encountering the target undergo scattering or reflection to increase each neutron's probability of causing fission (n, f) reactions in U-238. The U-238 can be deployed as one or more layers sandwiched between layers of neutron-reflecting material, or as rods surrounded by neutron-reflecting material. The gaseous fission products can be withdrawn from the irradiation chamber on a continuous basis, and the radioactive iodine isotopes (including I-131) extracted.