Epidemics of malaria have occurred in highland areas of East Africa since the 1980s, but the clinical spectrum of severe malaria in these areas has not been described. Over a 17-month period from 2001 to 2002, we assessed 117 consecutive patients admitted to Kabale Hospital in highland Uganda who met the World Health Organization 2000 criteria for severe malaria. Sixty-six persons (56.4%) were age 5 years or older, and 51 (43.6%) were under 5 years of age. Fever, vomiting, and cough were the most frequent symptoms. Hepatomegaly and splenomegaly were infrequent. Prostration was the most frequent manifestation of severe malaria in children under 5 years of age (45.1%) and persons 5 years or older (65.2%), followed by respiratory distress (29.4%) and severe anemia (19.6%) in children under 5 years, and respiratory distress (15.2%) and impaired consciousness (13.6%) in persons 5 years or older. Strictly defined cerebral malaria was uncommon (3.4%). In a multivariate regression model, children under 5 years were more likely than persons 5 years or older to present with severe anemia (OR 5.2, 95% confidence interval [CI] 1.2-21.9) and respiratory distress (OR 3.5, 95% CI 1.3-11.1) and less likely to present with prostration (OR 0.3, 95% CI 0.1-0.7) and impaired consciousness (OR 0.2, 95% CI 0.0-0.9). In highland Uganda, severe malaria often occurs in persons older than 5 years of age. "Typical" signs like splenomegaly are frequently absent, prostration is the major manifestation, and other manifestations vary in frequency according to age.