In this double-blind, within-patient vehicle-controlled study, patients with mild-to-moderate atopic dermatitis (AD) were treated for 3 weeks twice daily with pimecrolimus cream 1% on one forearm and with vehicle cream on the other forearm. Efficacy of treatment was assessed clinically using the Atopic Dermatitis Severity Index (ADSI), the Investigators Global Assessment (IGA) and the pruritus visual analogue scale. In parallel, blood microcirculation in the skin was measured as an objective parameter for skin inflammation. Skin hydration and transepidermal water loss (TEWL) were monitored as parameter relevant for the barrier function. Treatment with pimecrolimus cream 1% resulted in a quick and marked improvement of signs and symptoms of AD and a significant reduction of microcirculation from 33.90 to 15.55 AU (P < 0.0001). Skin hydration increased continually from 42.86 to 52.69 AU (P = 0.002) and TEWL decreased from 35.30 to 21.50 g/m(2)/h (P = 0.001), indicating restoration of skin barrier. At vehicle-treated sites changes of skin physiological parameters were less pronounced and observed only initially with later plateau or even reversal. At the end of the study, there were significant differences for all measured skin physiological parameters between pimecrolimus cream 1% and vehicle: microcirculation 12.15 AU (P = 0.004), skin hydration 7.12 AU (P = 0.002), TEWL 11.38 g/m(2)/h (P = 0.004). Non-invasive evaluation of microcirculation and barrier functionality thus represent a valuable tool for the objective assessment of treatment response to pimecrolimus cream 1%.