Antibacterial, antiparasitidal and antiviral properties have recently been 
attributed to members of the secreted phospholipases A(2) (sPLA(2)s) 
superfamily. Seven sPLA(2)s from groups IA, IB, IIA and III, were tested here in 
different culture conditions for inhibition of the in vitro intraerythrocytic 
development of Plasmodium falciparum, the causative agent of the most severe 
form of human malaria. In the presence of human serum, all sPLA(2)s were 
inhibitory, with three out of seven exhibiting IC(50)<0.1 nM. In all cases, 
inhibition could be induced by enzymatic pre-treatment of the serum. By 
contrast, no effect was observed when parasites were grown in a semi-defined 
medium (AlbuMAX II) devoid of lipoproteins and containing 10 times less 
phospholipids than the medium with human serum, strongly suggesting that 
hydrolysis of serum generating toxic lipid by-products, rather than a direct 
interaction of the sPLA(2) with the infected erythrocyte, is a general feature 
of the anti-Plasmodium properties of sPLA(2)s. Furthermore, in serum, six out of 
the seven sPLA(2)s were toxic against both trophozoite and schizont stages of 
the parasite development, contrasting with the trophozoite-selective bee venom 
enzyme's toxicity. Deciphering the molecular mechanisms at play in the 
phenotypic singularity of the bee venom enzyme toxicity might offer new 
prospects in antimalarial fight.