Aims. To determine the number and causes of deaths in methadone maintenance treatment (MMT). Design. Cross-sectional survey. Setting. New South Wales (NSW), Australia. Participants. Two hundred and thirty-eight patients who died while registered in MMT from 1990 to 1995. Measurements. Data on number and causes of death in MMT were obtained from data on file at the NSW Health Department, NSW Registry of Births, Deaths and Marriages, and NSW Department of Courts Administration. Findings. The most common cause of death was drug-related (44%), followed by medical illness (24%). Fifty deaths (21%) occurred in the first week of MMT, 88% of which were drug-related. In 92% of these drug-related deaths, there was evidence of polydrug use. In all, 42% of all drug-related deaths occurred during the first week of MMT. Nearly half the cases of drug-related death (46%) in the first week were noted by the medical practitioner at assessment to have a history of polydrug abuse or dependence. Four (9%) drug-related cases were prescribed doses of methadone in excess of the-then current national methadone clinical guidelines. Conclusion. The first 7 days of MMT is a high-risk period. Inadequate clinical review of subjects' tolerance to methadone and/or subjects' use of other central nervous system (CNS) depressant drugs probably contributed to most of these cases' deaths during induction. The findings from this study reinforce the importance of a thorough drug and alcohol assessment of people seeking MMT, cautious prescribing of methadone, frequent clinical review of patients' tolerance to methadone during induction and education about the dangers of additional drug use during this period.