This study compared the efficacy, tolerability, and safety of fluvoxamine, imipramine, and placebo in the treatment of panic disorder with or without agoraphobia. Fifty-four outpatients participated in the randomized, double-blind trial as part of a multicenter trial. After meeting inclusion criteria and completing screening requirements (e.g., laboratory testing, electrocardiogram, physical examination), patients were entered in a single-blind placebo washout phase. They were then randomized to either fluvoxamine, imipramine, or placebo. Measurements completed at each visit included the number and severity of panic attacks per week, the Sheehan Panic and Anticipatory Anxiety Scale, and the Clinical Global Impressions, and others. Results show that fluvoxamine is more effective than placebo and as effective as imipramine in reducing spontaneous panic attacks in moderate to severe panic disorder. However, starting doses of fluvoxamine and imipramine should be low to minimize untoward side effects (such as insomnia and agitation) and maintain compliance.