Reduced gap junctional intercellular communication (GJIC) occurs in neoplastic cells and contributes to their phenotype. Cyclic AMP agonists inhibit lung cancer cell growth and enhance GJIC in other cell types, but little is known about their effects on lung epithelial cell gap junctions. We have examined whether N-6,2'-O-dibutyryladenosine 3':5'-cyclic mono-phosphate (DBcAMP) affected GJIC, gap junction protein (connexin43) expression, and the growth of non-transformed and neoplastic mouse lung epithelial cells. DBcAMP (0.01-1 mM) stimulated GJIC (assayed by fluorescent dye microinjection) and connexin43 expression (assessed by Northern and Western blotting) and reduced their proliferation. These results suggest an association between cAMP growth inhibition and enhanced GJIC in lung epithelial cells.