When exposed to low CO2 levels, Chlamydomonas reinhardtii acquires the ability to accumulate CO2 to increase photosynthetic carbon fixation. A cDNA library has been constructed and screened to facilitate the identification of the different genes and proteins involved in this acclimation to low-CO2 conditions. The differential cDNA library screening led to the identification of several cDNAs up-regulated under low-CO2 conditions. One such cDNA shows homology to cyclophilins, a class of immunophilins with a peptidyl-prolyl cis-trans isomerase activity. This is the first report of an algal cyclophilin. In this report we study the changes in the C. reinhardtii cyclophilin transcript and protein levels during low-CO2 adaptation. Possible reasons for the increased cyclophilin expression in response to the drop in CO2 concentration are discussed.