Topical anesthetic agents are usually not effective on intact skin because of poor penetration. EMLA is a new topical anesthetic formulation consisting of a eutectic mixture of the local anesthetics lidocaine 5% and prilocaine 5%. We evaluated the ability of this preparation to prevent or ameliorate the pain associated with the percutaneous placement of large IV catheters. Under double-blind randomized conditions, either EMLA or placebo was applied to the dorsum of both hands and an occlusive bandage then placed over each application site. The creams were placed 30, 45 or 60 minutes prior to IV cannulation. A 16-gauge catheter was inserted through each application area. Patients were asked to evaluate the relative degree of pain at each venous puncture site. The EMLA site was preferred when the formulation was applied for 45 to 60 minutes prior to cannula placement (p less than 0.01, confidence limits for the binomial distribution). Cusum analysis confirmed this minimal effective application time. The results indicate that EMLA is an effective cutaneous anesthetic formulation when applied with an occlusive bandage for a minimal time period of 45 minutes.