Perfusion and fluorouracil (FU) accumulation were assessed using positron emission tomography (PET) with H2(15)O and 18FU in 36 patients with colorectal liver metastases. The tracers were injected intravenously and via the hepatic artery. Standard uptake values (SUV) were calculated using a region of interest (ROI) technique. The perfusion of non-tumorous liver tissue was similar after intravenous (i.v.) and intra-arterial (i.a.) assessment [mean of 2.67 (s = 0.61) and 2.2 (s = 0.45)]. Metastases were found to be hypoperfused compared to normal liver tissue after i.v. examinations [mean 1.73 (s = 0.77)]; i.a. injections revealed greater perfusion in metastases [mean 6.41 (s = 5.47)]. Single metastases showed up to 10 times greater perfusion with the i.a. injection route than with the i.v. one. However, lesions with no change or lower perfusion were also observed. Generally, accumulation of 18FU in metastases after i.v. infusion was less than after i.a.. Correlation of i.v. perfusion and uptake was moderate (r = 0.54, P = 0.0001); i.a. correlation was only slightly better (r = 0.61, P = 0.008). Perfusion as measured by H2(15)O-PET does not generally predict uptake of 18FU in colorectal liver metastases. To measure FU uptake using PET and 18F seems to be the most accurate method. It would allow one to identify individual patients with considerably greater accumulation of 18FU following i.a. administration who should profit from a cross-over to intrahepatic chemotherapy.