We identified 33 Malawians who had undergone total splenectomy for traumatic injury. We reviewed these and 33 controls by clinical and parasitological examination monthly for 1 year. Splenectomized patients (S) were 2.5 times as likely as controls (C) to complain about febrile symptoms during the month preceding a visit (P < 0.0001). They were nearly twice as likely as controls to have Plasmodium falciparum parasitaemia (S: 176/283 person visits; C: 86/262; P < 0.0001). Parasitaemia was more likely to be associated with febrile symptoms in splenectomized individuals (S: 104/176, 59%; C: 24/86, 28%; P < 0.0001). There were three deaths (two non-malarial, one unexplained) among splenectomized subjects and none in the control group. Parasite densities reached significantly higher levels, and mature parasite stages were more often seen in the peripheral blood, in asplenic individuals. In a partially immune population, asplenic individuals are at increased risk of malarial infections and illness. In a larger group without the benefit of regular review and prompt therapy, there may be an increased risk of life-threatening malaria. Splenectomy should be avoided when possible in an area with endemic transmission of P. falciparum.