Abstract Clozapine therapy has been associated with a high degree of urinary disturbances. The purpose of this study is to examine the effect of clozapine on urodynamic parameters and on the activity of the external urethral sphincter in anesthetized rats. Single cystometrograms (CMG) were performed on urethane-anesthetized female Sprague–Dawley rats, while also recording the EMG from the external urethral sphincter. Clozapine (0, 0.1, 1, 10 mg/kg) was administered intravenously. In addition, the peripheral end of the pudendal nerve was stimulated in order to determine if clozapine was exerting peripheral effects directly on the external urethral sphincter. Clozapine increased the bladder capacity while reducing the micturition volume thus resulting in a marked increase in the residual volume. The pressure threshold was increased but the peak pressure during contraction remained unchanged. The expulsion time and contraction time were decreased and the amplitude of the high frequency oscillations (HFO) seen during the expulsion phase were markedly reduced and even abolished. The EMG from the external urethral sphincter also showed marked decreases after clozapine, and the bursting pattern seen during HFO was abolished. Clozapine had no effect on the activity elicited from electrical stimulation of the pudendal nerve. Clozapine inhibits several urodynamic parameters and inhibits the activity of the external urethral sphincter in anesthetized rats. These effects may help explain the urinary disturbances reported in the clinical literature.