Impaired glucose tolerance and overt diabetes mellitus are becoming increasingly common complications of Cystic Fibrosis (CF), most probably merely as a result of increased life expectancy. In order to understand the pathophysiology of Cystic Fibrosis Related Diabetes (CFRD), knowledge on the possible expression and cell distribution of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein within the endocrine pancreas is required. In this report, we establish the first evidence for expression of CFTR protein in rat pancreatic islets by using three independent techniques. First reverse transcriptase-polymerase chain reaction (RT-PCR) amplification showed that CFTR mRNA is present in isolated Langerhans' islets. Furthermore, the analysis of flow cytometry separated islet cells indicated that the level of CFTR transcripts is significantly higher in the non-? than in ? cell populations. The expression of CFTR protein in rat islet cells was also demonstrated by western blotting and the level of expression was also found significantly higher in the non-b than in b cell populations, in complete corroboration of RT-PCR results. Last, in situ immunocytochemistry studies with two monoclonal antibodies recognizing different CFTR epitopes indicated CFTR expression occurs mainly in glucagon-secreting a cells.