Abnormalities in corticotrophin (ACTH) and cortisol levels before and after corticotrophin-releasing hormone (CRH) stimulation have been reported in depressed bipolar patients. The ACTH and free cortisol response to the injection of 100 micrograms of synthetic human CRH and plasma cortisol-binding globulin (CBG) levels were measured in 42 lithium-treated patients suffering from RDC bipolar-I disorder in remission, and in 21 age- and sex-matched control subjects. A 1-year follow-up was conducted in order to assess any possible relationship between outcome and the hormonal response. Bipolar patients showed higher baseline and peak ACTH concentrations than controls. A lower net area under the ACTH concentration curve after CRH stimulation predicted depressive relapse within 6 months by multiple regression analysis. The CRH challenge test could be a potentially good predictor of depressive relapse in remitted bipolar patients.