This study was undertaken to compare the in vitro responses of the portal vascular bed of normal and cirrhotic rat livers to a variety of vasodilator agents. Using carbon tetrachloride-induced cirrhosis in the rat as a model, isolated liver preparations were perfused via the portal vein with a synthetic medium (2.5% bovine serum albumin in Krebs-Henseleit buffer) to eliminate extrahepatic neural and humoral influences. Under these experimental conditions the mean perfusion resistance of the cirrhotic livers was approximately 117% higher than in controls (P less than 0.001). The vascular tone of the normal liver was minimal as assessed by the response to a variety of vasodilator agents, including sodium nitroprusside (3.0 X 10(-3) M), magnesium sulphate (6.0 X 10(-2) M), papaverine hydrochloride (6.4 X 10(-4) M), and cytochalasin B (6.3 X 10(-5) M). In contrast, these agents reduced the perfusion resistance of the cirrhotic livers by approximately 15%. Prostaglandin E1 (3.0 X 10(-6) M) and isoprenaline hydrochloride (2.4 X 10(-6) M) produced a lesser fall in resistance which nevertheless was greater in cirrhotic livers than controls. Cirrhotic livers, unlike the controls, were found to contain large numbers of myofibroblasts in perivenous and perisinusoidal locations. Previous studies have shown that myofibroblasts are capable of sustaining a high level of intrinsic tone and relax in response to vasodilator agents. It is concluded that part of the increased resistance to flow through the portal vascular bed of the cirrhotic rat liver in vitro is due to an increase in intrinsic vascular tone, possibly mediated via myofibroblasts, and can be reversed by pharmacological agents.