Chlamydomonas reinhardtii occupies a central position in cytoplasmic inheritance because it is the simplest organism that contains a chloroplast and non-Mendelian inheritance. Being unicellular and heterothallic, Chlamydomonas can be handled in the laboratory with the same ease as bacteria and yeast. The vegetative, haploid life cycle and the diploid meiotic sexual cycle can be physiologically controlled in large synchronous populations to facilitate either cell cycle biochemistry or genetic analysis. This chapter discusses the replication of the chloroplast DNA in vivo. Chloroplast replication usually is initiated 1–3 hours after the onset of the light period and continues for six hours, whereas nuclear DNA synthesis is initiated 2–3 hours into the dark period and continues for six hours. If cell division results in the production of four daughters, then two rounds of replication of chloroplast DNA synthesis precede two rounds of nuclear DNA synthesis. Both DNAs replicate by a semiconservative mechanism. Chlamydomonas does not appear to have dark repair reactions, so the chloroplast chromosome is stable over the entire cell cycle