Yohimbine is an alkaloid that has been encountered on the streets as an aphrodisiac, hallucinogen, dietary supplement and erectile dysfunction drug. Yohimbine hydrochloride is an alpha 2-adrenoreceptor antagonist, blocking the pre- and postsynaptic alpha-2 adrenoreceptors and causing an increased release of noradrenaline and dopamine. An average oral dose of 5-15 mg produces a therapeutic whole blood level range of 40-400 ng/mL. Overdoses leading to neurotoxic effects have been seen with blood concentrations up to 5,000 ng/mL. The laboratories from the Maricopa County Medical Examiner and the Los Angeles County Department of Coroner each encountered a case in which yohimbine was identified in whole blood by means of a liquid-liquid basic drug extraction with detection on a GC-MS. Because validated quantitative methods for yohimbine did not exist at either facility, both agencies referred the blood specimens to NMS Labs, Inc. The reference laboratory analyzed the blood specimens with an LC-MS-MS and determined the quantitative values of yohimbine to be 7,400 and 5,400 ng/mL. Given the absence of other significant positive findings and the substantial yohimbine blood concentrations cited, the respective Medical Examiners determined the cause of death to be acute yohimbine intoxication with the mode being an accident. Yohimbine is a rarely encountered drug in medical examiner casework, and interpretation of the results is difficult to assess toward the cause and manner of death without such case studies being described.