The effects of possessing non-functional genes for the enzyme cytochrome P450 CYP2D6 (CYP2D6) on mortality rate in humans was investigated in a study of post-mortem tissue (mostly liver tissue) from 15 ecstasy-related fatalities collected by pathology departments in England and Scotland. Fatalities were deemed to be ecstasy-related if MDMA, MDA, and/or MDE were detected in tissue. The ratio of functional to non-functional CYP2D6 genes was assessed in all tissue samples; poor metabolizers possess two non-functional CYP2D6 gene variants. Polymerase chain reaction (PCR) was used to type CYP2D6 gene variants. With the exception of one tissue sample that failed to produce detectable DNA, all samples (14 of 15) were typed for the normal version of the CYP2D6 gene and one variant, CYP2D6*4. Only 13 were typed for the other variant, CYP2D6*3. Variation in CYP2D6 genotype in post-mortem tissue was compared with gene variation in a sample of 662 controls residing in the UK. Only the normal copy of the CYP2D6 gene was detected in 9 of 14 post-mortem samples. One copy of CYP2D6*4 was detected in 4 of 14 samples, all from the Sheffield area, and one copy of CYP2D6*3 was detected in one sample from the Nottingham area. The presence of CYP2D6 variants in the post-mortem samples was not significantly greater than the percentage of non-functional CYP2D6 genes in controls (0.18 for ecstasy-related fatality sample, 0.25 in controls). None of the ecstasy-related fatalities were poor metabolizers. The authors conclude that CYP2D6 metabolism does not play a role in ecstasy-related fatalities in humans, a finding supported by other researchers (Kraemer and Maurer 2002; Kreth 2000; Pacifici et al. 2001). This includes reports from researchers who failed to find an increase in physiological or adverse effects in poor metabolizers given MDMA or MDE in laboratory settings (Kreth 2000; Pacifici et al. 2001). Since MDMA may saturate CYP2D6, all individuals may have lower CYP2D6 function after ingesting MDMA. Nevertheless, it is possible that an association between variance in CYP2D6 genotype and at least some MDMA-associated adverse events might be detectable with a larger sample of tissue or by including non-fatal cases in the analysis.