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Multi-directional interactions among the nervous, immune and endocrine systems have been demonstrated in both humans and nonhuman animal models for the last several decades. It has only become apparent in recent years, however, that behavior can exert profound influences on these interactions and they can, in turn, affect behavior (Ashley and Demas, 2017). For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors impinge upon immune-endocrine interactions. Reciprocally, immune-endocrine pathways can promote the development of altered behavioral states, such as sickness behaviors, anxiety, and depression. Although the field of psychoneuroimmunology (PNI) has traditionally explored these relationships from an applied, biomedical standpoint (Ader, 1981), the “immune-endocrine-behavior” nexus has been underappreciated in comparative species. It is becoming increasingly clear, however, that both ecological and evolutionary forces play a critical role in shaping neuroendocrine-immune crosstalk. The newly emerging field of ecoimmunology emphasizes the study of non-model systems from an ecological, evolutionary perspective, often under natural conditions (Demas and Nelson, 2012; Folstad and Karter, 1992; Sheldon and Verhulst, 1996). In contrast to PNI, ecoimmunology has focused less on the physiological mechanisms underlying behavioral responses, and more on the interactions between immunity and other life-history traits, both within and across individuals, populations, and species. It also emphasizes how these changes contribute to disease susceptibility across a wide range of animal species (often, but not exclusively, non-model systems). While both of these fields havemade fundamental contributions to our understanding of environmental-immune-behavior interactions, they have traditionally focused on different levels of analysis; whereas ecoimmunology traditionally focuses on ultimate questions (e.g., evolution and ecology of parasites and their effects on life histories), PNI more often emphasizes proximate questions (e.g., neural and endocrine factors that regulate stress, learning, immunity and disease).While ecological and evolutionary forces clearly drive the evolution, development, and production of immune responses, physiological mechanisms (e.g., hormone, neurotransmitters, cytokines) serve as the critical proximate mediators of these responses. We can no longer afford to ignore either aspect when attempting to develop an integrative, synthetic approach to the study of neuroendocrine-immune-behavior interactions and disease. To help promote a continuing synthesis of these important yet complementary areas of research, this special issue of Hormones and Behavior focuses on the theme of Neuroendocrine-Immune Interactions: Implications for Integrative and Comparative Physiologists with an