The seleno-organic compound ebselen showed anti-malarial activity in vitro against the murine Plasmodium berghei and the human P. falciparum. In P. berghei, the uptake and incorporation of [3H]-methionine and [3H]-adenosine was inhibited and the infectivity of plasmodia was reduced. Ebselen affects the development of asexual stages of chloroquine-resistant and -sensitive P. falciparum strains. Its IC50 for P. falciparum was about 14 mumol/l and that for P. berghei, about 10 mumol/l. The growth of P. falciparum was blocked by ebselen at all stages, including the invasion of erythrocytes by merozoites. In a human hepatoma cell line and in mouse peritoneal macrophages, no cytostatic or cytotoxic effects were found, indicating selective inhibition of plasmodia by ebselen. Its in vitro inhibitory effect is discussed in relation to its possible reactivity with thiol groups and its lack of an anti-malarial effect in infected mice.