Intraportal continuous infusion of 5-FU (600 mg/m2/24 h during 7 days) was administered in the immediate postoperative course of 6 consecutive patients with colorectal metastases resected for cure (one segmentectomy and 5 nonanatomical local resections). One month later, a systemic continuous infusion of 5-FU was delivered at the same dose. The tolerance of intraportal chemotherapy was good despite 2 patients with mild digestive toxicity. The plasma concentrations of both unchanged 5-FU and 5,6-dihydro-5-FU (the primary metabolite of 5-FU), were determined in 2 patients using Gas Chromatography--Mass Spectrometry. The 5-FU clearance was higher after intraportal infusion than after systemic infusion (x 1.5 to 3). Hepatic extraction was variable (0.32-0.70) and lower than in reported experimental data on dogs (0.90-0.99). 5,6-dihydro-5-FU concentrations were constantly higher than 5-FU concentrations in plasma. The patient with lower hepatic extraction had the higher 5,6-dihydro-5-FU plasma concentrations. These findings suggest a predominant extrahepatic formation of plasmatic 5,6-dihydro-5-FU.