In an attempt to establish the possible role of vasoactive intestinal peptide (VIP) in the regulation of vasomotor tone of coronary artery bypass grafts, this study examined the action of this peptide and the distribution of [125I]VIP binding sites in isolated human gastroepiploic artery (GEA), internal mammary artery (IMA) and saphenous vein. VIP (10(-10)-3 x 10(-7) M) elicited concentration-dependent relaxations in ring segments that were preconstricted with the thromboxane analog U46619. The maximal response was mean +/- SEM 79 +/- 4%, 52 +/- 8% and 23 +/- 3% of glyceryl trinitrate (3 x 10(-5) M)-induced maximal smooth muscle relaxation in the GEA, IMA and saphenous vein, respectively. Both receptor-binding and competition studies indicated that there was a higher density of [125I]VIP binding to smooth muscle cells of the GEA and IMA than to the saphenous vein. Total binding, at 50pM [125I]VIP, was 604 +/- 89, 381 +/- 64 and 87 +/- 12 amol/mg wet weight in the GEA, IMA and saphenous vein, respectively. Dense binding of [125I]VIP was associated with the tunica media in all the vessels studied. There was also binding to perivascular regions with no obvious binding to endothelial cells. These data demonstrate that arterial grafts, particularly the GEA, are more sensitive to the relaxant effect of VIP and this may possibly be due to a higher receptor density.