Recent studies have indicated that antiretroviral protease inhibitors may affect malaria disease outcomes by inhibiting the sequestration of Plasmodium falciparum-infected erythrocytes to CD36. We have investigated the antimalarial activities of 6 commonly used antiretroviral agents (Saquinavir, Ritonavir, Indinavir, Nelfinavir, Ampreavir, and Nevirapine). Our data indicate that in addition to their previously published effects on sequestration of P. falciparum-infected erythrocytes, the HIV-1 protease inhibitors saquinavir, ritonavir and indinavir directly inhibit the growth of P. falciparum in vitro at clinically relevant concentrations. The EC90 against P. falciparum for both saquinavir and ritonavir was below the level that these drugs reach in clinical use. While there are significant barriers to the use of these drugs for chemotherapy of malaria, these findings are particularly important given the high rate of malaria and HIV-1 co-infections in sub-Saharan Africa and the World Health Organization's "3 by 5" initiative. Work is currently underway to test these drugs for activity in a rodent model of malaria.