A death involving abuse of propylhexedrine and mitragynine is reported. Propylhexedrine is a potent α-adrenergic sympathomimetic amine found in nasal decongestant inhalers. The decedent was found dead in his living quarters with no signs of physical trauma. Analysis of his computer showed information on kratom, a plant that contains mitragynine, which produces opiumlike effects at high doses and stimulant effects at low doses, and a procedure to concentrate propylhexedrine from over-the-counter inhalers. Toxicology results revealed the presence of 1.7 mg/L propylhexedrine and 0.39 mg/L mitragynine in his blood. Both drugs, as well as acetaminophen, morphine, and promethazine, were detected in the urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the propylhexedrine heptafluorobutyryl derivative. Liquid chromatography-tandem mass spectrometry in multiple reactions monitoring mode was used to obtain quantitative results for mitragynine. The cause of death was ruled propylhexedrine toxicity, and the manner of death was ruled accidental. Mitragynine may have contributed as well, but as there are no published data for drug concentrations, the medical examiner did not include mitragynine toxicity in the cause of death. This is the first known publication of a case report involving propylhexedrine and mitragynine.