Arylpyrazine compounds are provided, including arylpyrazines that can bind with high affinity and high selectivity to CRF.sub.1 receptors, including human CRF.sub.1 receptors. The invention thus includes methods for treatment of disorders and diseases associated with CRF.sub.1 receptors, including CNS-related disorders and diseases, particularly affective disorders and diseases, and acute and chronic neurological disorders and diseases.