We have assessed the release of amethocaine from a new patch delivery system and subsequent drug diffusion through human stratum corneum and whole skin. We found that the patch system was more efficient than an amethocaine gel preparation. It was also observed, both in vitro and in vivo, that the stratum corneum acted as a reservoir for amethocaine. A double-blinded clinical trial, using 30- and 60-min application times, indicated that there was no statistical difference between patch and gel formulations in onset of percutaneous local anaesthesia. Furthermore, a 30-min application of the patch was sufficient to provide profound and prolonged topical anaesthesia in all volunteers. In contrast, although a 60-min application of EMLA was necessary to ensure satisfactory onset of percutaneous anaesthesia, the duration of action was much shorter than that of the amethocaine patch.