The binding of [3H]3,4-methylenedioxymethamphetamine [( 3H]MDMA) to both rat brain membrane preparations and glass fiber filter papers was analyzed in the present study. Saturation studies indicate that [3H]MDMA binding is saturable and monophasic in both the presence and absence of rat brain membranes. This apparent 'specific' binding of [3H]MDMA in both the presence and absence of brain homogenates was totally eliminated by pretreating glass fiber filter papers with polyethylenimine. Drug competition studies demonstrated that [3H]MDMA binding displays a distinct 'pharmacological' profile in the absence of brain tissue. These data indicate that apparent [3H]MDMA binding to rat brain homogenates results from artifactual of [3H]MDMA to glass fiber filter paper. In addition, uptake of [3H]MDMA into rat brain synaptosomes could not be detected. We conclude the [3H]MDMA has limited usefulness in radioligand binding studies.