Investigators studying the pathophysiological sequelae of bile duct ligation use different species of laboratory animals at varying postoperative times. There is also considerable variation in the type of control animal used for these experiments. In this study, we have attempted to validate our choice of the 3-day bile-duct-manipulated rat as the most appropriate control to study peripheral vascular neuroeffector mechanisms in bile-duct-ligated rats. We have compared the in vitro contractile response to norepinephrine in the absence and presence of cocaine, and the accumulation of the amine using 3H-norepinephrine of arterial rings and portal veins prepared from three different types of control rats--unoperated control, the 3-day bile-duct-manipulated and the 3-day pair-fed, bile-duct-manipulated rats. In vitro arterial reactivity to norepinephrine in the sham-operated rats was significantly attenuated and was associated with a cocaine-sensitive increase in norepinephrine uptake. Portal veins from the same animals showed no changes in in vitro reactivity to norepinephrine, although bile-duct manipulation and pair-feeding enhanced amine uptake. This study has demonstrated that bile-duct manipulation and pair-feeding attenuate in vitro vascular reactivity and enhance norepinephrine uptake. These in vitro changes are more pronounced in arterial tissue than venous tissue. In conclusion, these data indicate that bile-duct manipulation is the control of choice when measuring in vitro vascular neuroeffector mechanisms in 3-day bile-duct-ligated rats. Furthermore, these data emphasize the need to validate the control when experiments involving bile-duct ligation are undertaken.