<jats:title>Abstract</jats:title><jats:p>During the course of screening Ethiopian medicinal plants for their antimalarial properties, it was found that the dichloromethane extract of the roots of <jats:italic>Kniphofia foliosa</jats:italic> Hochst. (Asphodelaceae), which have long been used in the traditional medicine of Ethiopia for the treatment of abdominal cramps and wound healing, displayed strong <jats:italic>in vitro</jats:italic> antiplasmodial activity against the chloroquine‐sensitive 3D7 strain of <jats:italic>Plasmodium falciparum</jats:italic> with an ED<jats:sub>50</jats:sub> value of 3.8 µg/mL and weak cytotoxic activity against KB cells with an ED<jats:sub>50</jats:sub> value of 35.2 µg/mL. Five compounds were isolated from the roots and evaluated for their <jats:italic>in</jats:italic> <jats:italic>vitro</jats:italic> antimalarial activity. Among the compounds tested, 10‐(chrysophanol‐7′‐yl)‐10‐(<jats:italic>ξ</jats:italic>)‐hydroxychrysopanol‐9‐anthrone and chryslandicin, showed a high inhibition of the growth of the malaria parasite, <jats:italic>P. falciparum</jats:italic> with ED<jats:sub>50</jats:sub> values of 0.260 and 0.537 µg/mL, respectively, while the naphthalene derivative, 2‐acetyl‐1‐hydroxy‐8‐methoxy‐3‐methylnaphthalene, exhibited a less significant antimalarial activity with an ED<jats:sub>50</jats:sub> value of 15.4 µg/mL. To compare the effect on the parasite with toxicity to mammalian cells, the cytotoxic activities of the isolated compounds against the KB cell line were evaluated and 10‐(chrysophanol‐7′‐yl)‐10‐(<jats:italic>ξ</jats:italic>)‐hydroxychrysopanol‐9‐anthrone and chryslandicin displayed very low toxicity with ED<jats:sub>50</jats:sub> values of 104 and 90 µg/mL, respectively. This is the first report of the inhibition of the growth of <jats:italic>P. falciparum</jats:italic> by anthraquinone‐anthrone dimers and establishes them as a new class of potential antimalarial compounds with very little host cell toxicity. Copyright © 2005 John Wiley & Sons, Ltd.