To investigate the effects of vasoactive intestinal peptide (VIP) on Cl- transport across normal human bronchial epithelial (NHBE) cells grown in a monolayer, changes in short-circuit current (Isc) were measured in Ussing chamber systems. In the presence of 10-4M amiloride, the addition of VIP to the serosal solution led to an increase in the Isc in a concentration-dependent manner, the 50% effective concentration (EC50) being 2.6×10-11M. However, the addition of 10-5M forskolin had little effect on the increase in Isc. On the other hand, in the intracellular cAMP measurement, 10-5M forskolin remarkably increased the cAMP levels, but 10-7M VIP did not.This result suggests that Cl- secretion by VIP is not related to the raised intracellular cAMP levels in NHBE cells.