The study consists of a double-blind, randomized, placebo-controlled prospective 12 month maintenance on imipramine or placebo, followed by a 6 month discontinuation and drug/pill free phase in 80 panic disorder with agoraphobia patients who have shown good and stable response to open treatment with imipramine at the fixed weight adjusted dosage of 2.25 mg/kg/day in the preceding 6 months of active treatment. The first 80 patients to show marked response at both the 4 month and 6 month assessments of active treatment will randomly be assigned to maintenance on the same dose of imipramine or placebo with planned assessments every 2 months. Assessments will include demographic and clinical information and a comprehensive battery of clinician and patient ratings of the most salient major symptom domains of the disorder: panic, phobia and dysphoria/depression as well as operationalized and clinically relevant criteria of response and relapse. The specific aims of the proposed study are: 1) to assess the extent of reversals/relapse due specifically to withdrawal of imipramine over a 1 year period, 2) to assess the extent to which maintained improvement and response are specifically due to continued exposure to the pharmacological effects of pharmacotherapy, 3) to characterize imipramine's longterm effects by studying the relationship between symptomatology and plasma drug levels over the maintenance course. Thus, the study will assess the net beneficial effects of imipramine in maintaining the original improvement/response induced by the drug and will provide pilot data on the comparative rates of relapse after acute and maintenance treatment phases. In view of the chronic and fluctuating course of this disorder and the increasing numbers of patients who are effectively treated with imipramine or similar drugs, the results of the study should have important implications for the longterm management of panic disorder with agoraphobia patients, i.e., relapse and duration to relapse upon discontinuation of imipramine, risk-benefit ratio of maintenance treatment and compliance. In addition, the study extends our programmatic research in the characterization of imipramine's shorterm effects in this disorder.