Falciparum malaria is known to cause abnormalities in the liver. Hepatic metabolism in patients with falciparum was studied by caffeine clearance and the results were related to the severity of the disease. Caffeine (3.5 mg/kg) was administered orally to patients with severe (N = 10) or uncomplicated (N = 9) falciparum malaria. The plasma clearances during illness averaged 0.67 +/- 0.27 ml/min kg for the severe cases and 0.98 +/- 0.36 ml/min kg for the uncomplicated cases (P < 0.05). In the severe patients, clearances during illness (0.67 +/- 0.27 ml/min kg) were less than those in convalescence (2.15 +/- 0.91 ml/min kg) (P < 0.0001). However, in the uncomplicated cases, the clearances during illness and in convalescence were similar (P > 0.05) and clearance rates in convalescence were similar for the severe and uncomplicated cases (P > 0.05). Hepatic microsomal metabolism is apparently slow in severe falciparum malaria but reverts to normal in convalescence. Liver metabolic function does not appear to be significantly affected in uncomplicated malaria.