We report on cytotoxic effects of bcl-2 and bcl-xL antisense-oligodeoxynucleotides (AS-ODNs) in benign urothelial and transitional cell carcinoma (TCC) cell lines. The benign urothelial cell line (UROtsa) and four TCC cell lines (UM-UC-3, RT 112 , HT 1197 and T 24/83) were incubated with bcl-2 and bcl-xL AS-ODNs and cell mortality rates were assessed. Bcl-2 and bcl-xL AS-ODN treatment resulted in low toxicity in UROtsa cells (6% and 10% cell mortality, respectively). After bcl-2 AS-ODN treatment, cell mortality rates in TCC cell lines were significantly higher than in UROtsa cells (mean values: 33% vs. 6%, respectively). Bcl-2 AS-ODN treatment also caused significantly higher cell death rates in the majority of TCC cell lines when compared to bcl-xL-AS-ODN therapy (mean values: 33% vs. 11%, respectively). In conclusion, bcl-2 AS-ODNs show significantly higher cell mortality in TCC cells, whereas toxic effects on normal urothelium seem to be minor. Our results suggest favourable characteristics for the clinical application of AS-ODN in intravesical chemotherapy of TCC.