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Plasma tricyclic concentrations were assessed in 15 agoraphobic patients receiving combined imipramine and behavioral treatments. Imipramine but not N-desmethylimipramine plasma levels were found to significantly correlate with improvement. The results suggest that imipramine's effect in agoraphobia might be mediated predominantly through the serotonergic action of the parent drug. There was also suggestive evidence for differential antipanic and antiphobic-antidepressant effects. Implications for future studies of the mechanism of action of drug effects in agoraphobia are discussed.