BACKGROUND α,β-Thujone is a component of the essential oils of some plants including wormwood, sage, and cedar. It is used in herbal medicines, food and flavoring, and notably as the principal ingredient of the liqueur absinthe. We studied the effects of α,β-thujone on male and female rats and mice to identify potential toxic or cancer-related hazards. METHODS We deposited solutions containing α,β-thujone in methylcellulose through a tube directly into the stomach to groups of 50 male and female rats and mice five days per week for two years. Exposed rats received either 12.5, 25, or 50 milligrams of α,β-thujone per kilogram of body weight, and mice received 3, 6, 12, or 25 mg/kg. Control animals received methylcellulose with no chemical added by the same method. At the end of the study, tissues from more than 40 sites were examined for every animal. RESULTS All male and female rats receiving 50 mg/kg α,β-thujone died before the end of the study. All of those animals, and most receiving 25 mg/kg, experienced seizures. In male rats there was an increased incidence of cancers of the preputial gland and a slight increase in the incidence of pheochromocytomas of the adrenal gland. Nearly all male and female mice receiving 25 mg/kg α,β-thujone experienced seizures, and all of the female mice receiving 25 mg/kg died before the end of the study. No increases in cancers were observed in female rats or in male or female mice. CONCLUSIONS We conclude that α,β-thujone caused cancers of the preputial gland in male rats, and an increase in adrenal gland tumors in male rats may have been related to α,β-thujone administration. There was no increase in cancer incidence in female rats or male or female mice. Seizures were seen in almost all rats and mice receiving the highest doses of α,β-thujone.