To our knowledge, this is the first report of localized urticaria associated with intravenous methadone use. Methadone can, as do other opiates, induce release of histamine by degranulation of mast cells by a nonspecific mechanism (1–3). It remains to be established whether prophylactic treatment with antihistimine type-1 receptor antagonists can alleviate pruritus or urticaria. As demonstrated by this report, local urticarial reactions to intravenous methadone can be frequent. These reactions can be considered a severe side effect, but in the context of severe opiate addiction, this manifestation, with transient localized pain, was not an exclusion criterion. In this study, in which written informed consent was obtained, subjects with allergic manifestation could be switched to an oral preparation. We observed, however, that this change in method lasted not more than 3 days before patients returned to intravenous administration. Nevertheless, this type of reaction may represent a risk factor for lower participation in intravenous methadone programs and higher illicit opiate use.