Immune effector mechanisms can enhance the activity of antischistosomal drugs. We examined the in vivo effect of single oral doses of the antimalarials artemether (400 mg/kg) and mefloquine (200 mg/kg), recently described to have promising antischistosomal properties, against juvenile and adult Schistosoma mansoni in T cell-deficient and in comparably infected age- and sex-matched immunologically intact control mice. Artemether and mefloquine are equally effective in athymic and immunocompetent mice. Artemether treatment resulted in total and female worm burden reductions ranging between 71.1% and 85.3%, whereas mefloquine achieved total and female worm burden reductions of 80.4-97.8%. In conclusion, artemether and mefloquine act T-cell independently and no synergistic interaction with the immune response was involved.