The relaxant effect of a novel VIP analog, [Arg15,20,21Leu17]-VIP-Gly-Lys-Arg-NH2 was compared with that of the original VIP in the same guinea pig trachea precontracted by carbachol in vitro. The VIP analog caused significantly and concentration-dependent relaxation similarly to the original VIP. In contrast to the original VIP, the VIP analog demonstrated a slow onset and offset of action, with more than 90% of its maximum relaxation remaining 6 h after administration. Peptidase inhibition by captopril and phosphoramidon increased the relaxant effect and duration of action for original VIP but not for the VIP analog.