The cystic fibrosis transmembrane conductance regulator protein (CFTR) has been identified in bovine brain clathrin-coated vesicles, rat brain and a human neuroblastoma cell line using affinity-purified polyclonal peptide antibodies against CFTR. Immunocytochemical staining of multiple dendrites and soma of neurons of the diencephalon, midbrain, pons and medulla oblongata, has also been demonstrated. Whole cell lysates and membranes derived from rat brain, neuroblastoma cells and bovine brain clathrin-coated vesicles express the mature 150-165 kDa and 130 kDa unglycosylated forms of CFTR. The localization of CFTR to brain regions controlling homeostasis and energy expenditure may relate to the pathogenesis of non-pulmonary manifestations of cystic fibrosis. CFTR expression in neurons and coated vesicles suggests a possible effect on neuropeptide vesicle trafficking by mutant CFTR.