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To address the mechanisms underlying hatha yoga’s potential stress-reduction benefits, we compared inflammatory and endocrine responses of novice and expert yoga practitioners before, during, and after a restorative hatha yoga session, as well as in two control conditions. Stressors before each of the three conditions provided data on the extent to which yoga speeded an individual’s physiological recovery.A total of 50 healthy women (mean age, 41.32 years; range, 30–65 years), 25 novices and 25 experts, were exposed to each of the conditions (yoga, movement control, and passive-video control) during three separate visits.The yoga session boosted participants’ positive affect compared with the control conditions, but no overall differences in inflammatory or endocrine responses were unique to the yoga session. Importantly, even though novices and experts did not differ on key dimensions, including age, abdominal adiposity, and cardiorespiratory fitness, novices’ serum interleukin (IL)-6 levels were 41% higher than those of experts across sessions, and the odds of a novice having detectable C-reactive protein (CRP) were 4.75 times as high as that of an expert. Differences in stress responses between experts and novices provided one plausible mechanism for their divergent serum IL-6 data; experts produced less lipopolysaccharide-stimulated IL-6 in response to the stressor than novices, and IL-6 promotes CRP production.The ability to minimize inflammatory responses to stressful encounters influences the burden that stressors place on an individual. If yoga dampens or limits stress-related changes, then regular practice could have substantial health benefits.