There is no potent prognostic marker for recurrence in superficial bladder cancer at present. Thymidylate synthase (TS) is a key enzyme for pyrimidine synthesis. Dihydropyrimidine dehydrogenase (DPD) is an important pyrimidine salvage enzyme. We evaluated a combination of TS and DPD activities as a prognostic marker for recurrence in grade 1 and 2 superficial bladder cancer. The levels of TS and DPD activities in non-fixed fresh frozen bladder cancer specimens were determined biochemically by the 5-fluoro-2'-deoxyuridine 5'-monophosphate binding assay and the 5-fluorouracil degradation assay, respectively. Significantly, patients with low TS activity and high DPD activity had a longer post-operative tumor-free interval than those with either high TS activity or low DPD activity in the 2-year follow-up. There were no statistical differences observed in patient's sex and age as well as the histologic stage and grade of bladder cancer between the two groups. In addition, there is no correlation between TS and DPD activities. The present study suggests that a combination of TS and DPD activities may be an independent prognostic indicator for recurrence in grade 1 and 2 superficial bladder cancer, and that either high TS activity or low DPD activity predicts early recurrence.