The relation between the immune response and the clinical features of severe falciparum malaria was studied in Burundian adults with (n = 31) and without (n = 17) cerebral involvement. At the time of admission, mean values for age, temperature, and blood levels of hemoglobin, creatinine, bilirubin, and glucose were similar in the two groups. Plasma levels of tumor necrosis factor alpha, interferon gamma, interleukin 10 (IL-10), and soluble intercellular adhesion molecule 1 were similarly elevated in the two groups. Mean parasite counts and mean plasma levels of soluble E-selectin were higher in severe noncerebral malaria than in cerebral malaria and were correlated with each other. After adjustment for parasitemia, levels of soluble E-selectin remained higher in noncerebral malaria. All seven patients who died had cerebral disease. These patients had higher levels of creatinine, bilirubin, IL-10, and soluble E-selectin than did patients with nonfatal cerebral malaria. After adjustment for creatinine and bilirubin levels, IL-10 and soluble E-selectin concentrations were similar in fatal and nonfatal cases of cerebral infection. In these African adults, none of the immunologic variables investigated was specific to cerebral malaria or to a fatal outcome.