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The use of d-amphetamine pellet implantation as a method for producing rapid central drug tolerance was investigated. Mice were implanted with d-amphetamine pellets containing 2 mg of drug and were challenged 24 h later, a time when no detectable drug was present, with various doses of d-amphetamine i.p. Implantation was found to potentiate the stereotyped activity and produced tolerance to the exploratory activity induced by d-amphetamine. Daily pellet implantation for 3 days was not found to produce tolerance to the stereotyped activities. Animals administered a single pellet showed no difference in the brain disposition or metabolism of a subsequent dose of 3H-d-amphetamine. Twenty-four hour pellet implantation markedly increased the rate of conversion of 3H-tyrosine to 3H-dopamine (330%) and 3H-norepinephrine (61%) in the subcortex. However, this effect was reversed by the administration of 10 mg/kg of d-amphetamine.