Summary1. Administration of two doses of amphetamine HCl (5 mg/kg intraperitoneally) 45 min apart raised body temperature of rats by an average of 3.40 C and increased the turnover rate of brain 5-hydroxytryptamine (5-HT) by almost one-half. 2. Both effects were blocked by exposure to 40 C or by pretreatment with the B-blocker Ko 592 (1-(2-methylphenoxy)-3-isopropylamino-2-propanol), but not by the administration of the ganglionic blocker chlorisondamine combined with atropine. 3. Since it has previously been shown that hyperthermia per se increases the turnover rate of brain 5-HT, and that amphetamine does not directly affect the uptake and release of 5-HT in brain slices, it is concluded that the amphetamineinduced increase in 5-HT turnover may be secondary to the rise in temperature produced by the drug.