This study was designed to establish a possible relationship between the pharmacokinetics of 5-FU and response to treatment. Thirteen patients with advanced, histologically proven malignancies of the gastrointestinal tract were studied. 5-FU, at a single weekly dose of 15 mg/kg, was given in bolus or as an 8-h infusion to every patient. Plasma clearance of 5-FU after an i.v. bolus injection of 15 mg/kg was individually determined and found to vary widely among patients (from 0.39 to 2.55 l/min). A clearance greater than or equal to 0.86 l/min was seen in all the patients who did not respond to treatment. All patients (except one) with a partial response or a stable disease had a clearance less than or equal to 0.72 l/min. The mean clearance of non-responders (1.40 +/- 0.21 l/min) was significantly greater (P less than 0.02) than that of partial responders or patients with stable disease (0.73 +/- 0.15 l/min). These preliminary results deserve further investigation on a larger number of patients, before plasma levels of 5-FU may be accepted as an indication of response to chemotherapy.