Vasoactive intestinal polypeptide (VIP) and bombesin are peptides that have been identified in several mammalian tissues including skin. In this study, we have examined the actions of these peptides on forelimb vascular pressures, skin lymph flow, lymph total protein concentration and lymph total protein transport in the canine forelimb perfused at constant arterial inflow. Local intraarterial infusion of sequentially increasing infusion rates of VIP of 300, 600, and 1500 ng/min for twenty minutes at each infusion rate resulted in dose-dependent decreases in forelimb arterial pressures but no change in skin small vein pressure. At the two higher infusion rates, systemic pressure was significantly decreased whereas heart rate significantly increased. Skin lymph parameters were not a significantly altered with the exception of a small but significant decrease in lymph flow at the highest infusion rate of VIP. Infusion of bombesin at 500 ng/min for sixty minutes resulted in significant increases in forelimb arterial and systemic pressures, no change in skin small vein pressure and a significant bradycardia. Skin lymph flow, protein concentration and protein transport were not significantly changed during the infusion of bombesin. These data indicate that while VIP and bombesin possess potent vasodilator and vasoconstrictor effects respectively, they do not significantly affect transmicrovascular fluid and macromolecular efflux in the canine forelimb perfused at constant flow, as assessed by changes in lymph flow and protein concentration.