Repeated administration of amphetamine derivatives is reported to induce neurotoxicity in rat brain. Methamphetamine (MA) impairs the function of both the dopaminergic and serotonergic systems, 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) affects primarily the latter system. The neurochemical deficits induced by these amphetamines have been described in detail, but relatively few data have been reported regarding the behavioural consequences of the neurotoxic treatment. The aim of the present study was to investigate short- and long-term behavioural consequences of treatment with neurotoxic doses of (+)MA or (+)MDMA. Spontaneous locomotor activity in novel surroundings and cognitive function (avoidance behaviour) were evaluated. Rats were treated with four s.c. injections of 10 mg/kg (+)MA or (+)MDMA with a 2-hour interval between each injection. Behavioural tests were then carried out 3 days, 1, 2 and 4 weeks after these treatments. A reduction of spontaneous locomotor activity in novel surroundings was detected 3 days after the treatment with the study drugs, but not after 1, 2 and 4 weeks. No change in passive and active avoidance learning was observed. The lack of marked behavioural changes after a neurotoxic dose regimen indicates that some compensatory mechanisms may develop and counterbalance the neurochemical changes induced by these amphetamine compounds.