The pharmacokinetics of 5-fluorouracil (5-FUra) were investigated in 16 patients with metastatic colorectal cancer receiving high-dose folinic acid (LV 200 mg/m2) followed by 5-FUra bolus (400 mg/m2) and continuous infusion (600 mg/m2) on days 1 and 2. Quantitation of unchanged drug was assessed by a highly specific high-performance liquid chromatographic method. The concentrations of 5-FUra at the end of the loading dose averaged 30.7 +/- 13.2 micrograms/ml (i.e., 236 microM). The steady-state plasma concentration averaged 0.31 +/- 0.11 microgram/ml (i.e., 2.4 microM). 5-FUra plasma levels declined rapidly after the end of infusion with an apparent elimination half-life of 7.08 +/- 3.21 minutes. Clearance ranged from 776 to 3023 ml/min/m2. Large patient-to-patient variations in plasma 5-FUra concentrations were observed. No toxicity greater than WHO grade 2 was seen. One patient experienced grade 1 stomatitis and two others experienced grade 1 and 2 myelosuppression. One patient developed diarrhoea and another suffered asthenia. Nausea and vomiting were observed in 5 patients.