Data from treatment trials and biological challenge studies implicate involvement of both the serotonergic and the noradrenergic neurotransmitter systems in the pathophysiology of panic disorder. Mirtazapine, a newer antidepressant with a novel mechanism of action enhancing both norepinephrine and serotonin levels without reuptake inhibition, is a good candidate for the treatment of panic disorder. Ten adult outpatients with a primary diagnosis of panic disorder were treated openly with mirtazapine. Starting dose and titration were determined by individual clinical characteristics. Data on emergent side effects and clinical response were obtained at all follow-up visits, which typically occurred biweekly for 16 weeks. At the first follow-up visit (week 2-3), 4 of 10 patients met the criteria for response. Based on all available data, seven of the original sample demonstrated an acute response (defined as CGI = 2 or 3) by weeks 5-7, and six continued to have a positive long-term response at the 16-week end point. Side effects were reported by seven patients, with increased appetite and weight gain the most common. Prominent antihistaminic side effects such as sedation, enhanced appetite, and anxiolysis were often desired in the initial phase of treatment.