MDMA is a substituted derivative of methamphetamine that shares structural similarities with mescaline. Its combination of euphoric and psychedelic effects led to its adoption by the underground dance scene in the late 1980's. The Office of Chief Medical Examiner (OCME) investigates all unexpected, violent, and suspicious deaths in New York City. Toxicological testing is performed routinely on all autopsies and on selected external examinations. MDMA was identified in samples from 21 medical examiner autopsies and one external examination. There were three deaths in 1997, 3 in 1998, 11 in 1999 and 5 in the first half of 2000. The race of all the decedents was white, between the ages of 17-41 years (average age was 27) and 18 of the 22 deaths were men. Of these 22 deaths, 13 were due to acute drug intoxication, 7 due to mechanical injury (blunt trauma and gunshot wounds) and 2 due to a combination of natural disease and acute drug intoxication. Evidence of recent opiate and/or cocaine use was found in seven of the acute intoxication deaths and in none of the traumatic or combination natural/intoxication deaths. A review of case reports (45 reports) in the literature compared with New York cases showed similarities and differences. In both, the race of all decedents was white and the majority were young men. A majority of deaths in both cohorts occurred during or shortly after attendance at a club, party, or rave. One major difference with the literature group was the absence of MDMA deaths with co-intoxication with cocaine and/or opiates. This may be a reflection of substance abuse patterns in New York City compared to England, where most of the deaths in the literature took place. There is the expectation that physicians in the United States will observe an increasing number of patients who use MDMA. Physicians should be aware of the presentation and natural history of these conditions, the various management strategies and the high likelihood of co-intoxications including the possibility of life-threatening interactions with a wide range of medications. 4 Tables, 62 references