1. Electrical field stimulation (EFS) of muscle strips in vitro elicited a tetrodotoxin (TTX)-sensitive biphasic contractile response consisting of a phasic component followed by a tonic one. 2. The amplitude of both components of the response was impaired by N omega-nitro-L-arginine and potentiated by sodium nitroprusside. Cystamine caused a reduction in amplitude of both phasic and tonic components of the response to EFS. Neither N omega-nitro-L-arginine, sodium nitroprusside, nor cystamine induced changes in the resting muscle tone, or in the contractile response to exogenous agonists ATP and noradrenaline (NA). 3. The nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, induced a reduction in amplitude of both components of the response to EFS. 4. These results reveal a facilitatory prejunctional modulatory role for nitric oxide in sympathetic neurotransmission in rat vas deferens. Endogenous nitric oxide released in the extracellular space is presumed to potentiate neurotransmission by acting at prejunctional level via cGMP.