In vivo testing of Plasmodium falciparum sensitivity to chloroquine and sulfadoxine-pyrimethamine was carried out among asymptomatic school children from seven schools in four sub-counties in Hoima District in western Uganda. Seven hundred and twenty five children were screened, 487 (67%) had parasitaemia and 307 met the inclusion criteria. Full sensitivity to chloroquine in urban areas was found in 42%. Chloroquine resistance at RII level was observed in 46% (33-58%) and RIII level in 13% (0-24%). In rural areas, however, full sensitivity to chloroquine was found in 76% (70-84%). Resistance at RII and RIII level was found in 18 and 6% respectively. Full sensitivity to sulfadoxine-pyrimethamine was found in 98% and only 2% resistant at RII level. The relatively high proportion of chloroquine resistance at RII and RIII levels in urban areas could be attributed to easy access to chloroquine as well as frequent and probably inadequate use of chloroquine. Chloroquine can still be used as first line antimalarial drug in the area. Sulfadoxine-pyrimethamine should be the second line drug for cases not responding to chloroquine.