Plasmodium ovale is a common malaria parasite in Africa, but the epidemiology of P. ovale malaria is poorly known. Exposure to malaria, parasitemia, and morbidity were monitored for 6 years among the residents of a village in Senegal. The relationship between the level of P. ovale parasitemia and fever risk were analyzed, and diagnostic criteria for clinical P. ovale malaria were established. Then the relationships between the occurrence of P. ovale clinical malaria and a series of entomological, epidemiological, and genetic factors were investigated. There was no increased risk of fever when the P. ovale parasite count was <800 parasites/microL of blood. Of 6621 episodes of illness, 114 (1.7%) were attributable to P. ovale. Although most clinical episodes occurred during early childhood, a low incidence of the disease persisted among adults. Sickle cell trait carriers had increased susceptibility to the disease.