Expectations about health and disease induce immune and endocrine responses and directly affect health and treatment outcomes. However, there is an urge to understand the mechanical underpinnings how expectations affect immune and endocrine responses and how this knowledge can be used for therapeutic interventions.My research group studies the main expectancy learning mechanisms for itch and pain as a generic expectancy model across symptoms and conditions. We recently showed that dual expectancy learning processes (i.e. conditioning and suggestions) are most powerful for itch symptoms, corresponding with findings for other symptoms and conditions. Based on these studies, I propose a groundbreaking dual expectancy learning approach, testing whether combined expectancy learning processes (i.e. both conditioning and suggestions, offered with personalized cues and exposure to relevant stressors) affect most profoundly the immune and endocrine system, in turn affecting health and disease outcomes.The major aim is to unravel the central mechanisms of how peoples’ expectations affect immune and endocrine responses and related health outcomes, through the use of pioneering multidisciplinary methods in healthy and clinical populations. First, we systematically train immune and endocrine responses and relate them to psychological, neurobiological and genetic mechanisms. Second, we test these manipulations for physical health challenges (e.g. inflammatory or allergic histamine reactions) in healthy subjects and patients. Third, we study the long-term effects in chronic inflammatory itch and pain conditions (e.g. replacing anti-inflammatory pharmacotherapies, reducing side effects).This interdisciplinary, cross-boundary project progresses key theoretical knowledge of the central expectation mechanisms for immune and endocrine responses. Findings open new horizons for health prevention and therapeutic interventions for various inflammatory conditions and physical symptoms.