A randomized 14-day study in vivo compared the response of Plasmodium falciparum malaria to amodiaquine (35 mg/kg) and sulfadoxine-pyrimethamine (sulfadoxine, 25 mg/kg) in symptomatic outpatients at 2 sites in northern and western Kenya during 1993. Of the 239 patients recruited, 181 (76%) completed the study [84 (46%) on amodiaquine and 97 (54%) on sulfadoxine-pyrimethamine]. There were no significant differences in the parasitological, clinical or haematological responses between the 2 drug groups in both areas, with 18.5% resistance to amodiaquine versus 9.5% for sulfadoxine-pyrimethamine in the north and 35.1% against amodiaquine versus 34.5% for sulfadoxine-pyrimethamine in the west. In both sites defervescence was significantly more rapid with amodiaquine (P < 0.05) and true clinical failure (symptomatic illness with recurrent parasitaemia) was unusual (9%). As high-level resistance to chloroquine is widespread, both drugs are valuable alternatives. However, the significantly higher levels of resistance in the west may be a sign of the increased drug pressure in this holoendemic area and send an important warning concerning resistance to sulfadoxine-pyrimethamine.