An in vitro model system using COS cells that transiently express human plasma retinol binding protein has been set up in which we are able to mimic the retinol dependent secretion of this protein observed in hepatocytes. In the absence of its ligand, plasma retinol binding protein is retained in the endoplasmic reticulum. It contains a C-terminal sequence, RNLL, that could function as a cryptic KDEL motif and thus be responsible for its retention in the endoplasmic reticulum. The model system has been used to test a mutant lacking these four last amino acids for retention and retinol induced secretion. The results obtained show that although plasma retinol binding protein is retained in the endoplasmic reticulum, the RNLL sequence does not seem to be responsible for its retention.