Increased incidence of impotence is associated with some selective serotonin-reuptake-inhibitors (SSRIs), but the pathophysiological mechanism is unknown. Paroxetine and citalopram are extensively used SSRIs, but only paroxetine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determine the effects of paroxetine and citalopram on erectile function and NO production, in a rat model. Application of cavernosal nerve electrical stimulation produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, N(G)-nitro-L-arginine (0.3 mg x kg(-1)). Acute or chronic (2 weeks) paroxetine-treatment (10 mg x kg(-1)) reduced ICP-responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression.