In rats, stimulation of 5-HT_2C receptors caused inhibition of the micturition reflex, while stimulation of 5-HT_2A receptors caused activation of the external urethral sphincter (EUS); (Mbaki et al. 2005). However, in the guinea-pig using the selective 5-HT_2C receptor agonist Ro 60-0175, it was shown that stimulation of 5-HT_2C receptors caused activation of the EUS (McMurray & Miner, 2005). The present experiments were carried out to further investigate the effects of Ro 60-0175 on EUS-EMG activity, urethral pressure and the micturition reflex in the rat. Experiments were performed on spontaneously breathing female Sprague-Dawley rats (250-300g) anaesthetized with isofluorane (5% in 100% oxygen) and maintained with urethane (1.2 g kg^-1, i.v.). Simultaneous recordings of EUS-EMG activity, urethral and bladder pressures, and carotid arterial blood pressure were made. Micturition reflexes were evoked by saline infusion (0.1 ml min^-1) into the bladder. All substances were given as i.v. bolus doses. Changes were compared with vehicle controls for baseline EUS-EMG activity and urethral pressure by two-way ANOVA and the micturition reflex by unpaired Student’s t test. All values are expressed as means ± S.E.M. P < 0.05 was considered to be significant. Ro 60-0715 (300 μg kg^-1, n=5) caused a significant increase in baseline EUS-EMG activity and urethral pressure (22 ± 3 vs. 1 ± 1 V and 2 ± 0.2 vs. 0.1 ± 0.1 mmHg, respectively). The selective 5-HT_2C receptor antagonist SB 242084 (30 μg kg^-1, n=5) blocked the effects of Ro 60-0175 on EUS-EMG activity but failed to block the increase in urethral pressure. The 5-HT_2A receptor antagonists MDL 100907 and ketanserin (30 μg kg^-1, n=5) also blocked the effects of Ro 60-0175 on EUS-EMG activity but failed to block the increase in urethral pressure. Ro 60-0175 significantly increased bladder threshold pressure (5.7 ± 1.6 vs. 0.5 ± 0.9 mmHg), residual volume (0.2 ± 0.04 vs. 0.01 ± 0.01 ml) and volume threshold (0.4 ± 0.1 vs. 0.2 ± 0.02 ml). SB 242084 significantly decreased the effects of RO 60-0175 on bladder threshold pressure and volume threshold. MDL 100907 and ketanserin failed to block the effects of Ro 60-0175 on bladder threshold pressure, residual volume and volume threshold. These data indicate that activation of either 5-HT_2A or 5-HT_2C receptors can cause excitation of the EUS in the rat. The data above also confirms an inhibitory role of 5-HT_2C receptors in the control of micturition. However, the receptor subtype by which 5 HT₂ receptor agonists cause an increase in urethral pressure (Mbaki et al. 2005) remains to be determined. Interestingly in guinea-pigs and dogs it has been shown that 5-HT_2C receptor activation increases urethral pressure, which is more predictive for humans (Conlon et al. 2005).