Atovaquone (566C80), a hydroxynaphthoquinone, was investigated for activity against Plasmodium falciparum gametocytes (NF54 strain) in vitro. After 96 h of continuous exposure to the drug at 1.4 x 10(-7) M (a concentration achievable in humans 14 d after administration of a therapeutic dose of 10 mg/kg) reductions of 75%, 54% and 20% in the number of gametocyte stages 2, 3 and 4, respectively, were achieved. A small increase (14%) in stage 5 gametocytes was seen. At the same concentration, atovaquone showed greater activity against the asexual stages of P. falciparum, reductions of 93%, 96% and 43% in the number of rings, schizonts and trophozoites, respectively, being achieved. These data are consistent with inhibition of maturation of trophozoites. The observed effect on maturation of gametocytes is similarly consistent with blockade of gametocyte recruitment from merozoites produced by the preceding schizogony, or to stasis of intraerythrocytic sexual development before the formation of stage 2 gametocytes.