We investigated the effect of artemisinin on the rate of clearance of Plasmodium falciparum in patients with or without human immunodeficiency virus (HIV) co-infection. Initial mean (+/- SEM) parasite density was not different between HIV-infected and HIV-uninfected groups (27,486 +/- 2,643 versus 32,892 +/- 6,583, respectively; P = 0.55). The mean (+/- SEM) time to clear 75% and 90% of the parasites was 23.1 hr +/- 1.8 and 29.3 hr +/- 1.9, respectively, for the HIV seropositive patients compared with 16.0 hr +/- 1.4 and 20.8 hr +/- 1.4, respectively for the HIV seronegative patients (P = 0.0075 and 0.0026, respectively). By 32 hr, almost all (6/7) HIV positive patients remained parasitemic in contrast with 2/12 HIV seronegative patients. Moreover, the mean parasite density was almost 12-fold higher in the HIV seropositive patients than in the HIV seronegative patients at the same period (1789 +/- 616 versus 150 +/- 118, respectively; P = 0.0037). Overall, the mean parasite clearance time was 37.7 hr +/- 2.1 in the HIV seropositive group and 30.0 hr +/- 2.1 in those who were HIV seronegative (P = 0.0284). Whereas mean fever clearance time was 40.6 hr +/- 2.4 for the HIV seropositive group, it was 28.7 hr +/- 1.2 for those who were HIV seronegative (P = 0.0001). These observations are compatible with the hypothesis that the host's immunity affects the activity of antimalarial drugs, and our data suggest for the first time that clearance of P. falciparum after administration of artemisinin is delayed in patients with HIV co-infection.