Members of the tumor necrosis factor (TNF) superfamily have been revealed to be associated with painful bladder syndrome/interstitial cystitis (PBS/IC). TNF ligand-related molecule 1A (TL1A ) and its receptor, death receptor 3 (DR3), belong to the TNF superfamily and have been implicated in chronic inflammatory diseases. Bladder biopsies from 8 female patients clinically diagnosed with PBS/IC according to the National Institute for Diabetes and Digestive and Kidney Diseases criteria and 8 female bladder carcinoma control patients were investigated to test the protein and mRNA expression levels of ILIA and DR3 using western blotting and real-time RT-PCR. The protein level ratio of TL1A to beta-actin (IC, 0.65 +/- 0.03 vs. controls, 0.25 +/- 0.02, P<0.001) and of its receptor DR3 to beta-actin (IC, 0.66 +/- 0.06 vs. controls, 0.27 +/- 0.02, P<0.001) were observed to be significantly higher in the patients with IC. The real-time RT-PCR Delta Cts of ILIA minus GAPDH (IC, 7.60 +/- 0.52 vs. controls, 10.08 +/- 0.32, P<0.001) and the DR3 minus GAPDH (IC, 6.68 +/- 0.60 vs. controls, 8.99 +/- 0.61, P=0.017) were observed to be significantly lower in the patients with IC, suggesting that the mRNA levels of ILIA and DR3 were higher in the PBS/IC patients. The protein and mRNA expression of ILIA and DR3 are upregulated in the bladder tissues of PBS/IC patients and may be involved in inflammation and apoptosis in PBS/IC.