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Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] = 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] = 6.7, 95% confidence interval [CI] = 3.9-11.7), in children 1-7 months of age with tachypnea (OR = 8.8, 95% CI = 2.6-30.5) and dehydration (OR = 5.0, 95% CI = 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR = 4.7, 95% CI = 2.0-11.2) and inability to localize a painful stimulus (OR = 6.9, 95% CI = 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR = 2.1, 95% CI = 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume < 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.