We analyzed the clinical presentation of 800 severe malaria cases six months to 15 years of age (mean +/- SD = 4.3 +/- 3.0) recruited at the pediatric ward of the Ouagadougou University Hospital, and at the Sourou and Nayala District Hospitals in Burkina Faso. Inclusion criteria followed the World Health Organization (WHO) definition of severe and complicated malaria. The children were treated according to WHO guidelines with a complete regimen of drugs that were provided free of charge as part of the study. The case fatality rate of each sign and symptom of severe malaria was calculated on the 686 children whose outcomes were known. A total of 95 patients (13.8%) died while in the hospital; the mean +/- SD age of these children was 3.2 +/- 2.1 years. The age distribution and the clinical patterns of severe malaria was compared in patients from the urban areas of Ouagadougou characterized by relatively low transmission, and from rural areas where the mean inoculation rates are at least 20-fold higher. The mean +/- SD age of the urban and rural patients was 4.8 +/- 3.0 and 2.2 +/- 1.9 years, respectively (P < 0.001). The prevalence of coma was higher in the urban subsample (53.6% versus 28.9%; P << 0.001) while that of severe anemia (hemoglobin < 5 g/dL) was higher in rural patients (47.4% versus 14.8%; P < 0.001). Our data, in line with previous results obtained comparing rural areas characterized by different inoculation rates, show that the epidemiologic context influences the clinical presentation of severe malaria.