In the treatment of panic disorder double-blind controlled studies have demonstrated that imipramine (IMI) was effective at doses higher than 125 mg/ day. However a high rate of dropouts because of side effects has been reported in these subjects. In clinical settings, the administration of benzodiazepines (BDZ) in combination with IMI has been proposed to reduce the frequency and severity of side effects. In this naturalistic study, 49 patients affected by panic disorder with agoraphobia (n = 36) or without agoraphobia (n = 13) were treated with IMI plus lorazepam (LRZ) and followed for 12 months. The mean effective doses were 63.5 ± 35.5 mg/day for IMI and 2.4 ± 1.3 mg/day for LRZ. During the follow-up period, panic attacks disappeared in 75.5% of patients and 69.5% of agoraphobics were free of phobic avoidance. The patients with comorbid mood disorders and longer duration of illness required higher doses of both drugs. The combined treatment of IMI and LRZ allowed the use of low doses of the drugs, reduced the frequency and severity of the side effects and improved patient compliance. In fact, only 1 patient (2%) dropped out because of the severity of side effects. Furthermore, the patients who tapered LRZ treatment did not show BDZ withdrawal syndrom