The purpose of the present study was to assess and compare the therapeutic effects of imipramine during the initial treatment and retreatment of panic disorder with agoraphobia patients. Seven women with panic disorder with agoraphobia who had shown a marked and stable response to imipramine (121.4 +/- 41.8 mg/day) during their initial treatment of 24 weeks were retreated with the same dose (125 +/- 40.8 mg/day) of imipramine when they relapsed, on average 3 months following discontinuation of the drug. Assessments included operationalized criteria for response and relapse and plasma drug concentrations to verify treatment compliance. Data on phobic, panic, anxiety and depression measures were analyzed for 6 assessment times common to all patients; pretreatment, week 8 and 24 weeks follow-up of initial treatment, relapse which was also the beginning of retreatment, week 8 and 16-24 weeks follow-up of retreatment. At the end of retreatment all patients were marked responders and there was no significant difference on any outcome measure between the end of initial and retreatment assessment periods. However, overall therapeutic response to retreatment was slower than during initial treatment, in particular on phobic and patient rated panic measures. Although the full restoration of remission is clinically reassuring, the results caution that relapse may have sensitizing effects which delay, and if repeated could impede the response of panic disorder with agoraphobia patients to imipramine.