Clomipramine and imipramine treatments were compared in a sample of 152 panic disorders. Diagnosis was according to the positive criteria of DSM-III-R, but without exclusion of comorbid affective or personality disorders. The 2-year design provides non-blind treatment under typical clinical practice conditions, and it includes random assignment, periodic assessment with standardized measures, and comparable, flexible drug dosages. Findings on six outcome measures in the first 59 cases to complete 10 weeks showed both tricyclics to be markedly and equally effective for blocking panic attacks, alleviating phobic avoidance, and reducing nonspecific aspects of anxiety. Clomipramine's predominantly serotonergic action seemed not to determine a different action spectrum. During the first 2 weeks, clomipramine was significantly and unexpectedly superior to imipramine in both antipanic and antiphobic actions. These results require replication under double-blind conditions.