As methadone maintenance programs have expanded, there has been an increase in the number of deaths from prescribed and diverted methadone syrup. A cluster of 10 deaths caused the marked increase in the risk of fatal drug toxicity from methadone toxicity in the first 2 weeks of maintenance. The difficulty in determining starting doses is due to the overlap of potentially fatal with clinically effective doses. This overlap is due to wide variation in individuals’ response to methadone and the marked differences in new patients’ recent exposure and tolerance to opioids. The relationship of methadone dose with post-mortem blood concentration was investigated by summarizing data from 1994 New South Wales (NSW) coroner cases in a linear regression. The results of the study show that there was an identifiable linear relationship between weight-adjusted methadone dose and post-mortem blood concentration. This is despite the error introduced by the wide variation in the pharmacokinetics of methadone and inconsistent but significant post-mortem changes. Women given the same dose per kilogram had significantly higher post-mortem blood methadone concentrations than men. As expected, maintenance patients had higher post-mortem blood methadone concentrations than those that took only a single dose of methadone. While there seems to be a linear relationship between dose and post-mortem blood concentration, there is great inter-individual variation and perhaps a significant difference between males and females. It is concluded that, given the same dose of methadone per kilogram, the post-mortem blood concentration is likely to be two or three times greater than the trough plasma concentration in a living subject. 2 tables, 30 references