Photosystem I comprises 13 subunits in Chlamydomonas reinhardtii, four of which-the major reaction center I subunits PsaA and PsaB, PsaC and PsaJ-are chloroplast genome-encoded. We demonstrate that PSI biogenesis involves an assembly-governed regulation of synthesis of the major chloroplast-encoded subunits where the presence of PsaB is required to observe significant rates of PsaA synthesis and the presence of PsaA is required to observe significant rates of PsaC synthesis. Using chimeric genes expressed in the chloroplast, we show that these regulatory processes correspond to autoregulation of translation for PsaA and PsaC. The downregulation of translation occurs at some early stage since it arises from the interaction between unassembled PsaA and PsaC polypeptides and 5' untranslated regions of psaA and psaC mRNAs, respectively. These assembly-dependent autoregulations of translation represent two new instances of a control by epistasy of synthesis process that turns out to be a general feature of protein expression in the chloroplast of C. reinhardtii.