Summary Intrahepatic tumour is associated with alterations in splanchnic haemodynamics. To investigate the hypothesis that these are the result of a circulating vasoactive agent, rat small bowel segments were cross-perfused with arterial blood from groups (n = 12) of paired tumour-bearing (intrahepatic HSN sarcoma) and control rats. The vascular resistance of the segment was significantly greater during perfusion by tumour-bearing animals (91.6 mmHg ml-' min, s.e. 21.5, vs 51.7 mmHg ml-'min, s.e. 7.4, P<0.05), suggesting that intrahepatic tumour may be associated with a circulating vasoactive agent. A similar mechanism may underlie changes in the hepatic perfusion index in patients with liver metastases.There has been interest for several years in the haemodynamic changes that accompany the development of liver metastases from colorectal carcinoma, and their potential role-in identifying patients with occult metastatic disease. In 1985, Leveson et al. reported that the hepatic perfusion index (HPI), the ratio of hepatic arterial to total liver blood flow as measured by dynamic scintigraphy, was abnormally elevated in patients with colorectal liver metastases. This occurred both in patients with overt metastases and in those who, despite having an ostensibly normal liver at the time of primary surgery, manifested hepatic tumour within 1 year of follow-up. We have recently confirmed these findings using the more direct and quantitative technique of duplex ultrasonography (Leen et al., 1991;1993a).The mechanisms underlying this effect are unknown. Liver metastases derive their blood supply predominantly from the hepatic artery (Breedis & Young, 1954), and initially it was assumed that the primary change was an increase in hepatic arterial flow to meet demand from rapidly growing tumour tissue. Quantitative flowmetry has confirmed that hepatic arterial flow is increased, but has shown that a substantial reduction in portal venous blood flow also contributes to the elevation of the perfusion index (Leen et al., 1991). Experiments in rat liver tumour models have demonstrated a similar rise in the HPI that is due entirely to reduced portal venous inflow secondary to increased splanchnic vascular resistance (Nott et al., 1989;Hemingway et al., 1991;1993). This suggests that the means by which the tumour influences hepatic haemodynamics may not be purely local in nature. In the present study we cross-perfused normal rat bowel segments with blood from tumour-bearing and control rats, to investigate the hypothesis that the increase in splanchnic vascular resistance is due to a circulating vasoactive agent.Materials and methods Tumour was induced in male hooded Lister rats (200-250 g) by bilobar intrahepatic injection of 106 HSN sarcoma cells. Experiments were performed 3 weeks later, when discrete tumours were apparent. In a given experiment, one such animal, together with a weight-matched normal control rat, provided arterial blood to perfuse the intestine of a third (normal) rat.The experimental arrangement is shown in F...