The incidence and role of codeine in drug-related deaths in Victoria was investigated over a 5-year period. There were a total of 107 cases involving codeine, representing 8.8% of all drug-related deaths in this period in Victoria. There were only six fatalities in which codeine was considered the major poison. The mean (+/- SD) concentration of codeine in femoral blood was 4.0 +/- 2.3 mg/L (range, 2.1-8.0 mg/L). The mean concentration of free codeine was 1.3 +/- 0.9 mg/L (range, 0.4-2.8 mg/L). The remaining 101 cases involved a combination of codeine and other drugs. The mean total codeine blood concentration was 1.8 +/- 3.3 mg/L (range, 0.04-26 mg/L), which was significantly lower than in those cases where codeine was the major poison (p < 0.002). The mean concentration of free codeine was 0.82 +/- 4.9 mg/L (range, 0.02-9.0 mg/L), which was not significantly different (p > 0.05) from the six codeine-only cases. The most common drugs found in this group, other than codeine, were acetaminophen (62%), diazepam (46%), salicylate (20%), and ethanol (25%). The association of other psychoactive drugs in these deaths made the contribution of codeine difficult to assess. Free codeine concentrations > 0.4 mg/L and total codeine concentrations > 2.0 mg/L may be sufficient to cause death in the absence of any other contributing factors.