In order to investigate the effects of capsaicin on human detrusor contractility in both normal and spinal cord injury (SCI) bladders, a detrusor contractility study was performed in 10 normal and 8 SCI patients using isolated muscle strips. Eight bladder muscle strips were harvested from each patient undergoing surgery. Four strips were treated with capsaicin of 1-1000 microM, and electrical field stimulation and bethanechol were applied to the strips before and after capsaicin administration. The other four strips were pretreated with 40 nmole [D-Arg1, D-Trp7,9,Leu11]-Substance P (spantide) and then were underwent the same procedure. The results showed that capsaicin induced a dose-dependent increase in muscle tension on the human detrusor in both normal and SCI bladders. After treatment with varying concentrations of capsaicin for 10 minutes, low doses of capsaicin partially depressed detrusor contractility under both electrical and bethanechol stimulation while high doses of up to 1000 microM almost totally blocked detrusor contractility. The initial contractile effect of capsaicin was higher in normal bladders but the final depressant effect did not show any difference between normal and SCI bladders. With addition of spantide, the initial contractile effect and the final depressant effect of capsaicin remained the same, indicating that the contractile effects of capsaicin were not mainly through NK receptors but directly on muscle cells. Consecutive application of capsaicin to the same strip could not reproduce the contractile response. After washing free of capsaicin, the detrusor contractility under electrical stimulation and bethanechol was not reversible. A direct neurotoxic or cytotoxic effect could be found after high concentration capsaicin administration. In treating patients suffering from detrusor hyperreflexia using intravesical capsaicin instillation, this effect should be considered to prevent irreversible damage to the urinary bladder.