The long-term prophylactic effect of chemotherapy following transurethral electroresection of bladder tumors (TUR-Bt) was investigated using three different modalities: no prophylactic treatment (group C); oral UFT given at 1296 mg/day for 2 years (group U); and intravesical thio-TEPA at 30 mg/30 ml physiological saline, instilled 32 times over 2 years (group T). Patients newly diagnosed as having superficial bladder cancer (stage, less than or equal to pT1b; grade, less than or equal to G2) who had undergone TUR-Bt at Nara Medical University and its affiliated hospitals between November 1986 and March 1990 were allocated to one of the three groups by the envelope method. The initial treatment was maintained until the third recurrence or disease progression, except for TUR-Bt which was performed at the time of recurrence. The registered cases included 51 patients in group C, 50 in group U, and 52 in group T, and the number of evaluable cases in each group were 48, 47, and 45, respectively. The non-recurrence rates at 3 years were 54% in group C, 67% in group U, and 85% in group T, and the difference between groups T and C was significant. In terms of the tumor grade and stage, No significant difference was observed among the groups in the category of G1 or Ta tumors, but the non-recurrence rates determined in group T for G2 or T1 tumors were significantly higher than those obtained in group C. Moreover, no significant difference was found among the groups in relation to solitary tumors, but the non-recurrence rate obtained in group T for multiple tumors was significantly higher than that determined in group C. The overall cumulative recurrence rate in each group was 3.07 in group C, 1.95 in group U, and 0.70 in group T, and that determined according to tumor grade, stage, and multiplicity was also highest in group C, followed by group U and group T. The main adverse effects encountered were upper gastrointestinal (GI) symptoms (8.5%) in group U and irritable bladder (11.1%) in group T. Intravesical instillation of thio-TEPA tended to produce greater preventive efficacy than did oral UFT during the early postoperative period, but the prophylactic efficacy of thio-TEPA and UFT should be elucidated over a longer observation period.