Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was investigated for its in vivo efficacy in CD-1 mice infected with Plasmodium berghei. When orally administered at 50 mg kg -1 day -1 for 4 days, gedunin was able to suppress the parasitaemia level by 44%. However, no clear dose-response effects were observed in the 0-100 mg kg -1 day -1 dose range. Preliminary pharmacokinetics in Sprague-Dawley rats showed poor absorption. However, a binary treatment of 50 mg kg -1 day -1 gedunin with 25 mg kg -1 day -1 dillapiol, a cytochrome P450 inhibitor, increased parasitaemia clearance in mice to 75%. A clear dose-response was observed in the 0-50 mg kg -1 day -1 gedunin dose range when administration was combined with 25 mg kg -1 day -1 dillapiol. In addition, 7methoxygedunin, a semi-synthetic derivative which is more stable to degradation than gedunin, suppressed the level in mice by 67% at 50 mg kg -1 day -1 . When administered at this dose in combination with 25 mg kg -1 day -1 dillapiol, clearance increased to 80%. These results demonstrate the potential efficacy of antimalarial drugs and phytomedicines based on gedunin and the value of the combination therapy.