Scale-up of bioreactors has the intrinsic difficulty of establishing a reliable relationship among physical parameters involved in the design of the new bioreactor and the physiology of the cultured cells. This is more critical in those cases where a more complex operation of the bioreactor is needed, such as in photobioreactors. A key issue in the operation of photobioreactors is establishing a quantification for the interaction between external illumination, internal light distribution and cell growth. In this paper an approach to the scale-up of a photobioreactor for the culture of Spirulina platensis, based on a mathematical model describing this interaction, and the operation of a previous reactor 10 times smaller is presented. The paper describes the approach followed in the scale-up, the analysis of different design constraints, the physical realization of the new bioreactor design, innovative use of plastic material walls to improve reactor safety, and finally the corroboration of its satisfactory operation.