The efficacy of 5-fluorouracil (5FU) chemotherapy depends, in part, upon maintaining adequate intracellular levels of active metabolites. The uptake, distribution and elimination of 5FU and 5FU-anabolites were determined after an intravenous bolus infusion of 5FU, 15 mg kg-1, and the relationship between serum and tissue levels were evaluated. In six dogs samples of liver, pancreas, rectus abdominus muscle, blood, bile and pancreatic juice were collected at 0, 15, 45, 90 and 120 min. Bile and pancreatic juice levels of 5FU followed the same pattern as the serum, rising rapidly and falling exponentially, suggesting elimination by simple diffusion. Elimination of anabolites was more complex. Tissue levels of anabolites were highest in the liver and peaked later than in the pancreas and muscle. They were unrelated to serum levels of 5FU. The higher and more sustained levels of 5FU-anabolites in the liver may be responsible for some of the beneficial effects of 5FU chemotherapy on hepatic tumours.