In this study, we examined the possibility that 5-HT 1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and ␣-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT 1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT 1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men. intravesical pressure; external urethral sphincter-electromyography; urethral perfusion pressure; 8-hydroxy-2-(di-n-propylamino)tetralin; WAY-100635; serotonin SEROTONERGIC AGENTS, such as duloxetine, are clinically used to treat stress urinary incontinence (SUI) in women (14). Despite satisfactory results in most female patients, there are few reports regarding the effect of duloxetine on SUI in men. Because the incidence of SUI in men is dramatically lower than in women, SUI is generally considered to be a female issue (27,42). However, epidemiological studies have suggested that men are sometimes severely afflicted with SUI (27) and suffer greater emotional impacts than women (44). Currently, duloxetine has not been approved for treating SUI in men, but the drug has been used off label in some pilot studies; the studies (17,40,48) showed that the drug may produce a marked improvement in men with urinary incontinence.The rat model has now gained great popularity as the main species for developing pharmacologically based treatments of SUI. Effects of a 5-HT receptor agonist on regulatory bladder functions have been extensively investigated in female animals (5,6,15,19,23,28,43). To the best of our knowledge, few studies have explored the role of 5-HT 1A receptors in regulating urethral functions in male rats. In addition, many cases of sexually anatomic and functional dimorphism in the lower urinary trac...