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Optical laser isotope separation (LIS) and chemical process concepts are developed that arise in the large‐scale application of LIS processes with continuous process streams. The discussion applies to one‐photon, two‐photon and multiphoton LIS and the separation of a multiple‐component mixture. It is partly based on a novel reaction chamber which provides throughout its volume a constant energy fluence or power density. Concepts discussed are the isotopic depletion, isotopic and process selectivity, isotopic abundances, abundance quotients α* and β*, the photon utilization factor, and the material balance equations in the LIS plant. An expression is derived that gives the total process cost per unit separated product in terms of the isotopic selectivity, the isotopic depletion, and the natural abundance of the desired species. A total‐cost minimization is carried out which gives the optimum isotopic depletion of the process as a function of isotopic selectivity, photon cost parameters, and parameters characterizing the photochemical reaction and the feed costs. The expressions are applicable to ’’closed cycle’’ as well as ’’once through’’ feed processing. The results are used to estimate the cost per kg of heavy water as a function of laser efficiency and isotopic selectivity, for a formaldehyde‐based deuterium separation method.