BALB/c mice with established visceral infection caused by the intracellular protozoan Leishmania donovani were treated with oral atovaquone for 7 days. Treatment with 100 mg/kg of body weight per day was optimal and halted parasite replication in the liver. In mice treated with atovaquone, the effect of a suboptimal dose of pentavalent antimony was converted from partially leishmanistatic to leishmanicidal. These results demonstrate the in vivo antileishmanial effect of atovaquone and suggest a potential role for this oral agent in visceral leishmaniasis as an adjunct to conventional antimony treatment.