Anilide derivatives of the natural trioxane artemisinin were prepared and evaluated for antimalarial efficacy in Plasmodium berghei-infected mice. Selected anilides derivatives administered orally as one single-digit dose combined with mefloquine hydrochloride were completely curative, i.e., all 5 of the mice in the particular treatment group had no detectable parasitemia on day 30 post infection, gained as much weight by day 30 post infection as the control mice (no infection), and behaved normally.