The aim of this study was to investigate the efficacy and tolerance of capsaicin, a neurotoxin for C-fiber afferents, applied intravesically in the treatment of detrusor hyperreflexia. Eleven male and nine female patients who had spinal cord lesions caused by multiple sclerosis (12) or trauma (eight) resulting in detrusor hyperreflexia with urge incontinence and pollakiuria were randomized to receive one intravesical instillation of either 30 mg capsaicin in 100 ml 30% ethanol or 100 ml 30% ethanol alone. The patients were evaluated clinically (voiding diary) and urodynamically (maximum cystometric capacity, maximum detrusor pressure, first and normal desire to void) before and 30 days after the instillation. On day 30, the 10 patients who received capsaicin had significant decreases in 24-h voiding frequency from 9.3+/-6.1 to 6.7+/-3.8 (P=0.016) and leakages from 3.9+/-1.6 to 0.6+/-0.8 (P=0.0008); their maximum cystometric capacity increased from 169+/-68 to 299+/-96 ml (P=0.01) and maximum detrusor pressure decreased from 77+/-24 to 53+/-27 cm H2O. There were no significant changes in the control group. In seven subjects in each group, instillation triggered immediate side effects (suprapubic pain, sensory urgency, flushes, hematuria, autonomic hyperreflexia) that resolved within 2 weeks. Intravesical capsaicin significantly improves clinical and urodynamic parameters of detrusor hyperreflexia in spinal cord-injured patients. Side effects are frequent, tolerable, and identical to those induced by 30% ethanol alone.