The methionine residues in Tyr-corticotropin-releasing factor (CRF) and Tyr-sauvagine radioligands are subject to oxidation, which renders them biologically inactive. Therefore [Tyr 0 , Gln 1 , Leu 1 7 ]sauvagine (YQLS), in which the methionine was replaced with leucine was synthesized and labeled with 1 2 5 Iodine using chloramine-T. Mass spectroscopy revealed that chloramine-T-treatment did not oxidize YQLS. 1 2 5 I-YQLS bound with high affinity to cells expressing the murine CRF receptor 1 (CRFR1), CRF receptor 2 (CRFR2), and the mouse brain regions known to express both CRF receptors. 1 2 5 I-YQLS chemically cross-linked to CRFR1. In conclusion, 1 2 5 I-YQLS is oxidation-resistant, high affinity radioligand that can be chemically cross-linked to the CRF receptors.