Low-frequency right prefrontal repetitive transcranial magnetic stimulation (rTMS) appears to have antidepressant properties although the effectiveness of this treatment in clinical practice has not been assessed nor have the optimal stimulation parameters been adequately defined. A total of 130 patients with treatment-resistant depression were randomized to either 1- or 2-Hz rTMS over the right prefrontal cortex (PFC) for 2 wk with a possible further 2 wk extension. Non-responders were randomized to either 5- or 10-Hz left PFC rTMS. Overall, 66 patients (51%) achieved response and 35 (27%) remission criteria. For right-sided treatment, depression significantly improved but there was no between-group difference. Twenty-eight (42%) patients in the 1-Hz group and 33 (53%) patients in the 2-Hz group achieved response criteria (chi2=1.40, p>0.05). Depression symptom scores also improved for patients who crossed over to left-sided treatment but there was no significant difference in response between 5- and 10-Hz rTMS. Despite a heterogeneous sample, a significant proportion of patients met clinical response criteria following treatment but response to 1 and 2 Hz did not differ. 2-Hz right PFC rTMS has antidepressant properties but offers no advantage over 1 Hz despite doubling pulse number.