Previous experiments with rat isolated vas deferens have shown that sertraline pretreatment inhibits contractile responses to noradrenaline, KCl, serotonin and electrical field stimulation. In the present study, the aim was to investigate the effects of long-term use of sertraline on contractile responses of rat isolated vas deferens. Fifteen Sprague-Dawley rats were given long-term (21 days) sertraline treatment, while another 15 were used as control. Both vas deferens were excised. Epididymal and prostatic segments of each underwent electrical field and chemical stimulation (noradrenaline, serotonin, acetylcholine, adenosine-triphosphate). Epididymal and prostatic segments had different contraction characteristics. Long-term sertraline treatment inhibited contractile responses of vas deferens segments to electrical field stimulation. The responses to noradrenaline were amplified with a left shift on both segments. Responses to serotonin had only a left shift on epididymal segments, while no contractile responses were observed on prostatic segments of the groups. Long-term treatment with sertraline had peripheral effects on rat vas deferens contractility, and some of the effects may be through mechanisms other than the inhibition of serotonin re-uptake.