We studied the effect of jaundice on in vitro vascular reactivity to cumulative doses of norepinephrine (NE) by measuring the maximal response (Rmax) and the concentration of NE required to cause a 50% response (ED50) of isolated vascular smooth muscle. For this we prepared helically cut strips of thoracic aorta from bile duct ligated (BDL) rats at 1, 3, 6, 14, and 28 days postligation and compared them with those of nonoperated and sham-operated controls. From 1 to 6 days post-BDL, changes in liver blood chemistry and liver histology indicated cholestasis with necrosis. By 14 days, the tests for liver function and histology indicated a return to normal liver function and histology. In nonoperated controls, mean Rmax increased significantly from 883 +/- 67 mg of tension to 1220 +/- 68 mg of tension (P less than 0.0025) from 0 to 28 days, whereas ED50 remained unchanged. In sham-operated controls and BDL rats, an age-dependent increase in Rmax was also observed. However, in the sham groups, ED50 tended to decrease compared with nonoperated controls, indicating a surgically induced "sensitization" phenomenon of the vascular smooth muscle. In contrast, this was not seen in BDL rats since in these groups, the ED50 remained unchanged and significantly higher than in the sham groups, in both the jaundiced (1-6 days) and nonjaundiced (14-28 days) period. Furthermore, these changes occurred in the absence of any alteration in portal pressure. These changes may be important in understanding the mechanism of hypotension and shock in postoperative patients with obstructive jaundice even after the jaundice has been relieved.