Two CRF receptors, designated CRF-RI and CFR-RII, exhibit distinct brain localizations.Two forms of CFR-RII, designated CFR-RIIalpha and CFR-RIIbeta, result from alternative mRNA splicing. Urocortin, an additional member of the CRF family, shares 63% sequence identity with urotensin and 45% sequence identity with CRF. Urocortin specifically binds to and activates CRF-RI and CRF-RII, but binds to CRF-RII more efficiently than CRF, suggesting that it may be the true, high affinity ligand for the CRF receptor type II.