Initially the hypothalamic factor responsible for the release of corticotropin (CRF), was thought to be a simple peptide^1–6. More recent work has led to the conclusion that CRF is a multifactorial complex^7–9. In 1979 we proposed¹⁰ that vasopressin, much disputed as a CRF candidate, was a major constituent of the complex, interacting with and potentiating the CRF activity of the other component(s). The recent characterization of a 41 residue ovine hypothalamic peptide capable of releasing adrenocorticotropic hormone (ACTH) in a dose-related manner¹¹ has allowed us to compare its CRF bioactivity with that of vasopressin and simple extracts of the hypothalamus, and to investigate any interaction it may have with vasopressin and other hypothalamic factors in the release of ACTH. We report here that the new CRF is more potent than vasopressin in releasing ACTH. When given simultaneously with vasopressin a fourfold potentiation of CRF activity with steep dose–response characteristics was observed. It also potentiated vasopressin-free hypothalamic extracts, suggesting that the new CRF does not account for all the non-vasopressin portion of the CRF complex.