New antimalaria drugs are needed on the background of increasing resistance to chloroquine. This study was undertaken to elucidate whether other membrane stabilizers than chloroquine have anti-malarial activity in vitro. We here report the anti-plasmodial activity of chlorpromazine (CPZ) and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol. As a screening method we used a modified Desjardins' 3H-hypoxanthine assay. The IC50 = 50% inhibition of 3H-hypoxanthine uptake was found at 1.028 ng/ml = 3.2 microM CPZ, 758 ng/ml = 1.6 microM trans(E)-clopenthixol and 436 ng/ml = 0.9 microM cis(Z)-clopenthixol. The inhibitory effect of trans(E)-clopenthixol in these low concentrations on Plasmodium falciparum in vitro seems particularly promising, since it is known that trans(E)-clopenthixol has no neuroleptic effect.