OBJECTIVE: The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks. METHOD: Twenty-one outpatients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam (mean dose = 2.2 mg/day) and were then randomly assigned to receive either supportive drug maintenance and slow, flexible drug taper or an identical medication treatment plus 12 weeks of concurrent, individual cognitive behavioral treatment. Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended. RESULTS: Twenty subjects completed the study. There was no significant difference between groups in the rate of alprazolam discontinuation (80% and 90%, respectively, in the alprazolam-only group and the combined treatment group). However, during the 6-month follow-up period, half of the subjects who discontinued alprazolam without cognitive behavior therapy, but none of those who were given cognitive behavior therapy, relapsed and resumed alprazolam treatment. CONCLUSIONS: Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation. The results warrant further research on the thoughtful integration of these two therapeutic modalities.