Aims. Buprenorphine at high dosage became available in 1996 for substitution treatment in France. This drug is considered particulary safe and has become widely available in general medical practice. We investigated the possible implication of a buprenorphine-benzodiazepine association in six deaths of known abusers. Design. Full investigation of cause of death was conducted for six drug abusers. Setting. The deaths occurred in two regions of France (Auvergne and Lorraine). Assays were carried out by the Institut de Medecine Legale at Strasbourg, France, one of the few French laboratories equipped to assay buprenorphine. Measurement. First, the blood and urine underwent triple exhaustive screening. Secondly, buprenorphine and norbuprenorphine were analysed in all the autopsy samples by HPLC/MS. Findings. Benzodiazepine-buprenorphine associations were found in every case; no other substances that could account for the death were found. The tissue concentrations were markedly higher than the blood levels. Conclusion. If the number of deaths linked to such drug misuse proves high, it may be necessary to review how buprenorphine is dispensed.