In both rats and mice a single large dose of methylenedioxymethylamphetamine (MDMA; 25 mg/kg i.p.) caused a fall 3 h after injection in the content of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, a fall in noradrenaline in hippocampus and cerebellum, and a rise in dopamine (DA) but fall in dihydroxyphenylacetic acid (DOPAC) in striatum. These effects were transient, levels being essentially back to normal by 24 h after injection. Repeated large doses (3 x 25 mg/kg in 24 h) of MDMA caused a large long-lasting fall in the content of 5-HT and 5-HIAA in cortex in rats but had only a slight effect in mice. Increasing the dose to 3 x 50 mg/kg in mice produced a large long-lasting fall in striatal DA. The analogue MDEA(3,4-methylenedioxyethylamphetamine) caused a similar slight fall in 5-HT but in contrast to MDMA caused a slight rise in DA content in mice. The nature and degree of neurotoxicity with methylenedioxyamphetamines appears to be drug and species-specific.