Juvenile rheumatoid arthritis (JRA) is characterized by chronic inflammation of the joints. In the present study we demonstrate that exposure of JRA patients to a noradrenergic stressor (cold pressor test) results in enhanced LPS-induced IL-6 production by peripheral blood cells of these patients. Healthy, age-matched controls had the same rise in norepinephrine, but do not respond with changes in IL-6 production after exposure to the cold pressor test. Moreover, PBMC of patients with JRA express mRNA encoding alpha(1)-adrenergic receptors (AR), predominantly of the alpha(1d)-AR subtype. In contrast, we could not detect mRNA encoding for alpha(1)-AR in PBMC of healthy controls. The results of this study suggest that expression of alpha(1)-AR mRNA in PBMC during chronic inflammation is associated with altered responses of the immune system to stress.