Atopic dermatitis is a stress-responsive disorder that involves the autonomic nervous system. The current study used heart rate variability to examine the effect of itch, scratching and mental stress in atopic patients with moderate to severe disease. Twenty-one patients with active disease and 24 healthy volunteers participated in the study. Heart rate variability measurements were taken at 5 min intervals at rest and after each of 3 acute stress tests, which included histamine-induced itch at the forearm, scratching around the itch site, and the Trier Social Stress Test. Atopic patients displayed a higher heart rate than healthy controls in all 4 experimental settings, which was statistically significant using Cohen's delta analysis. The very low frequency component of the power spectrum, indicative of sympathetic activity, showed a 200% increase after scratching in patients with atopic dermatitis. The high frequency component, reflecting parasympathetic tone, responded swiftly to itch and scratching in healthy controls, but displayed a limited adaptability in atopic dermatitis. This study supports the concept that atopic dermatitis is a stress-responsive disorder and involves autonomic nervous system dysfunction. Atopic subjects exhibited an overactive sympathetic response to itch and scratching, while the parasympathetic tone was persistently and rigidly elevated, showing a lack of adaptability in response to stress.