Alprazolam is one of the most widely prescribed benzodiazepines in the United States. It is generally considered a safe and effective drug for the treatment of anxiety disorders and panic attacks. Few overdoses that are due to the sole ingestion of alprazolam have been reported. This paper documents a fatality due to alprazolam intoxication and describes the distribution of alprazolam and an active metabolite, alpha-hydroxyalprazolam, in tissues obtained at autopsy. Qualitative identification of the drugs was achieved by full-scan gas chromatography-mass spectrometry, and quantitative analysis was performed by high-performance liquid chromatography. High concentrations of alprazolam were found in all specimens analyzed, but the metabolite was detected only in subclavian blood, urine, bile, and liver. A postmortem heart blood alprazolam concentration of 2.1 mg/L is the highest reported in the literature to date.