OBJECTIVE To assess the role of neuropeptides in the control of vascular tone in the human saphenous vein the actions of substance P, vasoactive intestinal peptide, calcitonin gene related peptide, neuropeptide Y, and somatostatin on this blood vessel were examined. METHODS In vitro organ bath techniques were used with preparations of saphenous veins obtained from 29 patients (aged 41-66) who were undergoing coronary bypass surgery. RESULTS Substance P, vasoactive intestinal peptide, and calcitonin gene related peptide relaxed pre-constricted vessels in a dose dependent manner with a rapid onset of action, taking one to two minutes to reach a plateau at each dose. Substance P (10(-9) to 10(-6) mol/l) induced relaxation with a maximum response (mean (SEM)) 23.0 (6.6)% of the total relaxation induced by glyceryl trinitrate 1 microgram/ml and a 50% maximal effective concentration of 6.8 x 10(-9) mol/l. Vasoactive intestinal peptide (10(-10) to 10(-7) mol/l) produced a relaxation of 27.0 (5.1)% at 10(-7) mol/l. The maximum responses induced by substance P and vasoactive intestinal peptide were significantly reduced, to 3.7 (2.8)% and 4.7 (2.0)% respectively, after removal of the endothelium. Calcitonin gene related peptide (10(-10) to 10(-7) mol/l) elicited only 14.3 (2.6)% relaxation at 10(-7) mol/l, and this was not affected by removal of the endothelium. By contrast, neuropeptide Y and somatostatin exerted concentration dependent constriction on resting vessels. Neuropeptide Y (10(-10) to 10(-7) mol/l) caused prolonged contraction (roughly 20 minutes to reach a maximum plateau at each dose). At 10(-7) mol/l, the constriction amounted to 28.0 (12.0)% of the response to 90 mM KCl, in ring segments with or without endothelium. Somatostatin (10(-10) to 10(-6) mol/l) quickly caused contraction with a maximum response of 42.7 (15.0)% and a maximum response of 42.7 (15.0)% and a 50% maximal effective concentration of 6.7 x 10(-6) mol/l. The constriction was greatly increased when endothelium was removed, with a maximum response of 78.2 (16.8)% and a 50% maximal effective concentration of 4.3 x 10(-7) mol/l. CONCLUSIONS Vasoactive peptides have diverse effects on the vascular tone these effects are endothelium dependent. The exact physiological role and implication for performance of bypass grafts require further investigation.