Intravesical chemotherapy has been well established as an effective therapy for recurrent superficial bladder tumors. We investigated the role of flow cytometry as a predictor of tumor recurrence/progression after intravesical chemotherapy. Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 'cold cup' biopsy samples of 52 patients with primary superficial bladder cancer. Cell suspensions, retrieved after mechanical fragmentation, were stained with propidium iodide and examined on FACScan flow cytometer. Clinical follow-up ranged from 3 to 57 months with a median of 20 months. Of the 52 patients, 24 aneuploid and 28 diploid tumors were observed. The degree of ploidy in relation to histological grade showed an increasing frequency of aneuploid pattern in grades 2 and 3 but with no statistical significance. 17.8% of diploid tumors versus 54.1% of aneuploid tumors recurred (p less than 0.05). 12.5% of the aneuploid tumors progressed. No progression among diploid tumors was observed. Of the 52 patients examined, 35 (16 aneuploid and 19 diploid) were treated, after TUR, with intravesical prophylactic therapy. Epirubicin in 24, mitomycin C in 4 and recombinant interferon alpha 2a in 7 were used. 50% of aneuploid tumors versus 10.5% of diploid tumors recurred (p less than 0.05). Strong predictors of response to intravesical prophylaxis of recurrence were G1 grade and diploid DNA content.