An emerging literature indicates that dispositional positive affect (PA) may play a protective role in health and render individuals less susceptible to inflammatory diseases. In this regard, it has been suggested that PA is associated with diminished activation of innate immune pathways. To explore this possibility, we examined relationships between trait positive emotional style, as assessed by the Positive and Negative Affect Schedule, and monocyte-derived lipopolysaccharide-induced production of the pro- and anti-inflammatory cytokines, interleukin (IL)-6, IL-1beta, TNF-alpha, and IL-10, among 146 healthy adults aged 30-54. After controlling for demographic factors and other covariates (age, gender, race, body mass index and white blood cell count), hierarchical regression analyses revealed an inverse association between trait PA and stimulated production of IL-6 (DeltaR(2)=.03, b=-.18, p <.04) and IL-10 (DeltaR(2)=.09; b =-.32, p <.01), with the latter association obtained only in men. No association was observed between trait PA and stimulated IL-1beta or TNF-alpha. Additionally, trait negative affect was unrelated to any of the stimulated cytokine levels. These initial findings suggest that individuals higher in trait positive emotional style show decreased in vitro production of the early inflammatory mediators IL-6 and IL-10 in response to stimulation with endotoxin which may confer protection against the emergence and progression of inflammatory diseases. Further exploration of this potential psychophysiological pathway is warranted.