EMLA cream is a topical formulation based upon the eutectic mixture of lidocaine and prilocaine and is used in clinical settings to produce local analgesia after application under occlusive dressing. A blanching reaction has been reported to occur locally after application, but it is not clear whether this reaction is caused by the anesthetic mixture, by the vehicle or the occlusion. We studied this blanching reaction in 50 healthy volunteers in a double-blind randomized assay: EMLA versus placebo, under occlusive dressing for 1 h, each subject being his own control. We found 33 cases (66%) of blanching after application of EMLA cream versus 3 cases (6%) after placebo, this difference being highly significant. Blanching was observed without delay, after removal of the dressing, and was very transient, disappearing in less than 3 h in all cases. We thus conclude that the blanching reaction is (1) frequent but very transient, and (2) determined by the anesthetic mixture included in EMLA cream and not by the vehicle alone, nor by the occlusion, since it is not found with the placebo. The precise mechanism of this reaction is unknown.