The effects of protirelin [thyrotropin-releasing hormone (TRH)] administration on the release of thyrotropin (TSH) and prolactin (PRL) were examined in 14 patients with panic disorder prior to and during chronic treatment with imipramine. During imipramine treatment, the patients exhibited an increase in their TSH response to TRH (delta delta max TSH = 3.65 +/- 6.02 mu IU/ml, p less than 0.05) and in their PRL response to TRH (delta AUCPRL = 734 +/- 965 ng/ml/45 min, p less than 0.005). Several behavioral measures correlated with the neuroendocrine measures during imipramine therapy. These preliminary findings might suggest a role for changes in dopaminergic function in the clinical effects of imipramine in patients with panic disorder.