The skin lining the ear canal is rigidly adhered to the underlying bone and cartilage and is very vulnerable to mechanical damage, such as a scratch; it can become inflamed and the vasodilation or neovascularization provoked by the inflammation makes it more capable of absorbing drugs. The poorly vascularized tympanic membrane is covered by skin similar to that of the external auditory canal; however, it is reduced to a fine layer of epidermis and is less fit for rapid drug absorption. The possibility of a murder via auris was known to occur in 16th-century Italy,5 and it was based on the knowledge of that time about the direct absorption of some substances from the ear. Pliny in his Natural History (Book 25.4.17), published in English in 1601, recommended pouring oil of henbane into the ears for use in earache, though he warns that it may cause mental disorder. Henbane was an official drug mentioned in old English pharmacopeias and dispensatories and it was used as well as the cannabis extract in the form of eardrops in the treatment of earache.5,17 Many years ago, Macht2 demonstrated with experiments in animals that certain poisons, including scopolamine, can be absorbed through the intact ear and often likewise skin eruptions and shorten the coagulation time of blood.(quoted in 3) It is hard, however, to accept that, in this way, such a quick poisoning would take place. On the other hand, the tympanic membrane can be perforated and the highly vascularized middle ear is connected to the pharynx by the eustachian tube. Something similar happens with intoxication by atropine contained in eyedrops, where the drug passes by way of the lacrimal duct toward the nose and is eventually swallowed.7 Chronic otorrhea was not uncommon in Shakespeare's times4 and there are indications that physicians of that time might have known that fluids in the middle ear could pass into the pharynx and that a substance instilled into an ear with a tympanic perforation could find its way to the pharynx and be swallowed. The work of Bartolommeo Eustachio (ca 1520-1574) was known. His detailed description, the Opuscula Anatomica, published in Venice in 1563, includes the differences between the bony and cartilaginous portions of the tube, a description of the nasopharyngeal opening, and a description of the tensor tympani muscle.(quoted in 4,5) The effective concentration in plasma of scopolamine is very low: 40 pg/mL is necessary for its therapeutic effects, and up until a few years ago, 0.5 mg was injected during preanesthesia.2 The proportion of alkaloid in dried leaves and seeds of henbane is relatively high, ranging from 0.045% to 0.6%.18 Although we do not know either the concentration used by the murderer or the rate of absorption of the drug, a few milligrams of the drug instilled into the ear may reach toxic levels in the blood. Thus, the ampoule containing the henbane that Claudius poured into King Hamlet's ear could very well have contained sufficiently high enough amounts of scopolamine so as to fulfill his lethal mission.