Cyclophilins are cyclosporin A sensitive peptidyl-prolyl cis-trans isomerases found in the cytoplasm of a wide range of species from Escherichia coli to man. Cyclophilin homologues are translocated into mitochondria, the endoplasmic reticulum and the bacterial periplasmic space. Here, the nucleotide sequence of a non-essential fifth Saccharomyces cerevisiae cyclophilin homologue encoded by chromosome XII is presented. As expected from its hydrophobic signal sequence and a hydrophilic carboxy terminus ending in the tetrapeptide HDEL, epitope-tagged cyclophilin D was found associated with the endoplasmic reticulum.