The activity of lysophospholipase of human erythrocytes increased by about 3 orders of magnitude upon infection with Plasmodium falciparum. The apparent Km for hydrolysis of lysophosphatidylcholine by this enzyme was 50 ± 7μM and the apparent Vmax 6·8±0·6 nmol/h × 106 cells. The activity was Ca2+ independent and had a broad pH maximum at pH 8. The enzyme was insensitive to such anti-malarials as mefloquine and arteether and was only weakly inhibited by chloroquine, with a 50% inhibition concentration (IC50) of 70 mM. The anti-malarials quinine and quinacrine were more efficient inhibitors, with IC50s of 2·6 mM and 0·7 mM, respectively. The sulphydryl agents p–hydroxymercuribenzoate (pHMB) and thimerosal were considerably more potent, inhibiting the plasmodial lysophospholipase with IC50s of 18 μM and 10 μM, respectively. When present at 10 μM prior to invasion, both pHMB and thimerosal arrested the growth and reinvasion capacity of P. falciparum in culture. In a synchronized P. falciparum culture the continuous presence of 5 μM thimerosal dramatically decreased total parasitaemia and, within 4 days, totally abolished the capacity of the surviving parasites to reinvade. Thus the plasmodial lysophospholipase may represent a potential new target for anti-malarial chemotherapy.