Repetitive electrical field stimulation evoked muscle contractions of the isolated mouse detrusor strips, which could be abolished by tetrodotoxin (TTX). Both Mn2+ and Ni2+ (0.01-0.06 mM) enhanced neurogenic detrusor contractions in high Ca2+ (5 mM) medium. The non-cholinergic component of the evoked detrusor contractions (in the presence of atropine) was specifically sensitive to this enhancing effect by either Mn2+ or Ni2+. In contrast, the cholinergic component in alpha,beta-methylene ATP-treated detrusors remained unaffected. As compared with Mn2+ and Ni2+, other metal ions, Cu2+, Co2+, Cd2+ and UO2(2+), failed to enhancing the non-cholinergic component of neurogenic detrusor contractions. Nitric oxide synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester and 7-nitroindazole (a selective neuronal NOS inhibitor) markedly inhibited the enhancing effect by either Mn2+ or Ni2+ on the neurogenic detrusor contractions. Moreover, Mn2+ and Ni2+ did not affect the contractions induced by either carbachol or alpha,beta-methylene ATP. It is concluded from these findings that the neuronal NOS-NO generation pathway is apparently involved in the enhancing effect of Mn2+ and Ni2+ on the muscle contractions elicited by excitatory non-cholinergic neurotransmission in the mouse detrusor strips.