Deletion of phenylalanine 508 (DeltaF508) is the most prevalent disease-causing mutation resulting in retention of the immature CFTR in the endoplasmic reticulum. The most common strategy to induce the delivery of DeltaF508-CFTR to the surface of cells is by reducing the incubation temperature ( approximately 28 degrees C). Cell surface biotinylation of HEK293T cells grown at 37 degrees C for 48h, confirmed the presence of mature wild-type CFTR, but not DeltaF508-CFTR at the cell surface. On the other hand, cells incubated at 28 degrees C for 16h showed both mature and immature DeltaF508-CFTR at their surface. The trafficking of immature DeltaF508-CFTR, but not mature DeltaF508-CFTR, to the cell surface occurred at low temperature even upon addition of BFA, suggesting the involvement of a Golgi-independent pathway. These results suggest that low temperature induces the appearance of a mix population of mature and immature CFTR molecules at the plasma membrane through distinct pathways.