The hypoalgesic effect of EMLA cream (Eutectic Mixture of Local Anesthetics) applied for 5, 15, and 30 min on facial skin was evaluated. Hypoalgesia was assessed by changes in pain thresholds to brief argon laser stimuli 0, 2, 5, 10, 15, 20, 25, 30, 45, and 60 min after removal of EMLA cream. The local cutaneous vascular changes induced by EMLA cream was evaluated by Erythema Index determined by reflectance spectroscopy and by laser Doppler blood flowmetry. A large inter-individual variability in analgesic efficacy was observed. The volunteers could be divided into two groups, one group of 6 persons where EMLA induced analgesia or considerable hypoalgesia, and one group of 4 persons where EMLA had no or only slight hypoalgesic effect. This great variability should be considered when EMLA cream is used for facial application in the clinic. Differences in local blood flow probably contribute to the variability. Application of EMLA cream for 5 and 15 min did not change erythema of the skin, while 30 min of application caused minor blanching.