The efficacy of indomethacin and acetaminophen as antipyretics was compared in 43 febrile patients with uncomplicated falciparum malaria. Each patient was randomly assigned to receive low oral doses of indomethacin (25 mg three times a day) or acetaminophen (1000 mg four times a day) as well as mefloquine. Oral temperature was measured before dosing and then every 4 h until apyrexia. Indomethacin was significantly quicker at clearing fever than acetaminophen (P < 0.05) and at reducing excessively high fever (> or = 39 degrees C) to a safer range (< 39 degrees C). No adverse effects were observed in either treatment group. The study shows that indomethacin is a potent antipyretic agent. It appears to be a safe alternative to acetaminophen for the treatment of febrile malarial patients who may benefit from antipyretic medication, including those unresponsive to treatment with acetaminophen.