Venlafaxine is a phenethylamine derivative that has recently been approved for use in the treatment of depression. It is chemically unrelated to tricyclic, tetracyclic, or other available antidepressant agents. Anticholinergic, hypotensive, hypertensive, and cardiotoxic side effects are rare. Two fatal cases encountered at separate laboratories are discussed, both involve high levels of venlafaxine. Concentrations of the drug in peripheral blood, heart blood, urine, vitreous humor, and liver are reported. Descriptions of extraction and gas chromatographic methods for confirmation and quantitation are included.