Previous studies have shown that Fischer 344 (F344) and Lewis (LEW) rats may differ with respect to their behavioural and neurochemical responses to several drugs of abuse, including amphetamines. Herein, we have examined whether such strain differences extend to a ring-substituted amphetamine, namely 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), a recreationally-used drug endowed with euphoric, but also long-term neurotoxic effects. Beside strain differences in baseline locomotor activity (F344>LEW), it was found that the subcutaneous administration of 10 mg/kg, but not 5 mg/kg, MDMA increased locomotor activity in F344 rats only. On the other hand, such a treatment increased to similar extents extracellular dopamine (DA) levels in the nucleus accumbens of F344 and LEW rats, thus suggesting that genetic differences in MDMA locomotor effects are not accounted for by accumbal DA release.