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(-4) M 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 x 10(-11) M. However, the addition of 10(-5) M forskolin had little effect on the increase in Isc. On the other hand, in the intracellular cAMP measurement, 10(-5) M forskolin remarkably increased the cAMP levels, but 10(-7) M VIP did not. This result suggests that Cl- secretion by VIP is not related to the raised intracellular cAMP levels in NHBE cells.