Buprenorphine at high dosage became available in France in 1996, as a substitution treatment for heroin addicts. Since this date, numerous deaths were attributed to this drug. This paper reports two original series of 39 and 78 fatalities involving buprenorphine observed at the Institute of Legal Medicine of Strasbourg and at 13 other French forensic centers, respectively. The files were recorded from January 1996-May 2000. The first 20 fatalities that were previously published were excluded from this epidemiological study. From these 117 subjects, 96 were male (82%). Buprenorphine and its primary metabolite norbuprenophine were assayed in post-mortem blood by HPLC/MS (n=11 labs) or by GC/MS (n=3 labs). Blood levels for buprenorphine ranged from 0.5 to 51.0ng/ml (mean 10.2ng/ml) and 0.1 to 76ng/ml (mean 12.6ng/ml) in Strasbourg and the other centers, respectively. Blood levels for norbuprenorphine ranged from 0.2 to 47.1ng/ml (mean 8.2ng/ml) and <0.1 to 65ng/ml (mean 10.6ng/ml) in Strasbourg and the other centers, respectively. The mean values appear to be within the therapeutic range. Buprenorphine was identified in 24 of the 26 hair samples assayed in Strasbourg, at concentrations ranging from 10 to 1080pg/mg. Intravenous injection of crushed tablets, a concomitant intake of psychotropics (especially benzodiazepines and neuroleptics) and the high dosage of the buprenorphine formulation available in France appear as the major risk factors for such fatalities. In addition, two suicide-related deaths were also observed, with blood buprenorphine concentrations at 144 and 3276ng/ml.