The combination chemotherapy of 5-FU (CIV) and low-dose CDDP (IV) was applied to 15 patients with advanced or recurrent adeno-or squamous cell carcinoma. Schedules for treatment were as follows: A: 5FU 320 mg/m2/day for 28 days with 7 mg CDDP/m2/day for 5 days/weekx4. B: 5FU 320 mg/m2/day for 28 days with 3.5 mg CDDP/m2/day for 5 days/weekx4, C: after B, 7 mg CDDP/m2/day/every 3 or 4 days. Serum CDDP concentrations were measured by flameless atomic absorption spectrophotometry. In all patients, a tendency to accumulation of total CDDP was observed. No severe side effects (> or = grade 3) were observed in patients given B therapy. We previously reported that there was no significant difference between A and B therapy in anti-tumor effects. The peak total CDDP concentrations were 1000 or more than 1000 ng/ml in A therapy, and 500 to 1000 ng/ml in B (with the exception of a case) therapy. These results demonstrated that B therapy could maintain the anti-tumor effect and decrease the severity and frequency of side effects, suggesting that the optimal serum concentration of total CDDP might be between 500 and 1000 ng/ml.