Oral treatment of phantom limb pain in five males and two females ranging in age from 25 to 78 years with sub-hallucinogenic doses of Iysergic acid diethyImaide (LSD-25) resulted in improvement in pain in five patients and reduction in use of analgesics. In two of the five patients improvement was striking and in the other three, pain and analgesic use were reduced moderately. LSD treatment was ineffective in two patients. Intravenous infusion or bolus injection of LSD-25, 10ngml at 0.5 mlmin. resulted in facilitation of 5-HT venospasm. The findings suggest that LSD-25 facilitation of 5-HT activity occurs centrally consistent with the hypothesis of the central nature of phantom limb pain.