When expressed heterologously in cultured epithelial or nonepithelial cells,∆ F508 CFTR is found as an immature, core-glycosylated species localized by immunofluorescence microscopy to the ER membrane, whereas wild-type CFTR is predominantly found as a complex glycosylated species at the plasma membrane (4). CFTR immunoreactivity is restricted to internal membranes in sweat ducts from∆ F508 CFTR homozygotes (7), although recent studies suggest that the degree to which∆ F508 CFTR is detectable at the plasma membrane may be tissue-specific (8). These findings led to the initial assignment of∆ F508 CFTR as a class II, or trafficking, mutant (2). Further study of the function and fate of this mutant protein indicates that the trafficking model is incomplete. As discussed below, folding defects in∆ F508 CFTR biosynthesis alter the protein’s interactions with the quality control system in the early secretory pathway and also directly or indirectly affect its activity as an anion channel and its stability as a cell surface glycoprotein. Thus,∆ F508 should be regarded not as a simple class II mutant, but as a mixed mutant with the properties of classes II, III, and IV.