This study was undertaken to determine whether clinical methods for preservation and storage of hearts explanted for transplantation affect the responsiveness of coronary arteries to vasoactive agents. Porcine hearts were perfused with crystalloid or blood cardioplegic solution. Rings of coronary arteries were suspended in organ chambers for measurement of isometric force (1) immediately after perfusion and (2) after 5 hours' storage of the hearts at 4° C in the same cardioplegic solution (n = 6 in each group). The maximal contraction of the smooth muscle to potassium chloride, 40 mmol/L, was reduced significantly after perfusion with crystalloid cardioplegic solution (10.8 ± 1.2 gm) compared with blood cardioplegic solution (17.3 ± 0.8 gm) and nonperfused coronary arteries (control group 16.9 ± 1.8 gm). The sensitivity of the arteries with endothelium to the contractile effects of prostaglandin F(2α) increased after perfusion with crystalloid cardioplegic solution (ED50, [-log mol/L] 5.8 ± 0.04) compared with blood cardioplegic solution (5.3 ± 0.02) and the control group (5.7 ± 0.03). In addition, relaxations to the calcium ionophore A23187, bradykinin, and the α2-agonist BHT-920, which depend on the presence of endothelial cells, were significantly reduced after perfusion with crystalloid compared with blood cardioplegic solution or the control group. The responsiveness of the endothelium and smooth muscle after 5 hours' cold storage was unaltered in the blood cardioplegia group, whereas storage resulted in functional recovery in the crystalloid cardioplegia group, with the result that all groups were comparable. These data suggest an immediate and reversible change in vascular function with crystalloid cardioplegia, which was not apparent with blood cardioplegia.