The purpose of this study was to characterize the electrostimulation-induced relaxation in guinea pig urethral rings. From sacrificed male guinea pigs, urethral rings were cut between the bladder neck and the penile crura and mounted in an in vitro bath. The drop in baseline tension in response to electrical stimulation (rectangular pulses of 0.8-msec pulse duration, a frequency of 3, 5, 10, and 20 Hz, and 75-mA current) was measured in the presence of various pharmacologic agents. In urethral tissue precontracted with 10(-5) norepinephrine, a significant relaxation of 34.8% was found at 10 Hz. This relaxation was not affected by the addition of neuropeptide Y (NPY, 10(-8)-10(-6) M), 10(-6) M atropine, 10(-5) M alpha-beta-methylene-adenosine,5'-triphosphate (alpha-beta-methylene-ATP, a purinergic antagonist), and tolazoline (alpha2 antagonist, 10(-8)-10(-4) M). However, with the alpha1 antagonist prazosin (5 x 10(-8)-5 x 10(-7) M), no relaxation occurred. The tissue response was of neurogenic origin as it was blocked by 10(-7) M tetrodotoxin. Norepinephrine-precontracted urethral rings of male guinea pigs exhibit a relaxation response at 10 Hz that is alpha1-adrenergic, non-cholinergic, non-purinergic, and independent of NPY.