This study was carried out in the village of Faladié, Mali located in the malaria-endemic Kati region, two years after routine use of chloroquine prophylaxis was discontinued in children 0 to 9 years old. The main purpose of this study was to assess changes in chloroquine resistance. Two cross-sectional surveys in association with WHO in vivo chloroquine sensitivity testing were conducted, i.e., one in September 2000 and one in December 2002. Findings in 2000 showed that 77.5% of mothers administered chloroquine prophylaxis to their children in compliance with physician orders. The plasmodic index was 62%. The overall level of parasitologic resistance (based on the 1996 WHO in vivo tests) was 80%. The overall therapeutic failure rate was 17.5%. Findings in 2002 demonstrated a plasmodic index of 28%, an overall parasitologic resistance rate of 45% (based on WHO in vivo tests), and an overall therapeutic failure rate of 15%. The diminution of resistance in 2002 may be due to the decrease of drugs pressure and to low exposure of individuals to mosquitoes at the end of transmission season. Althougt these data indicate a 44% drop in chloroquine resistance (P=0.0001), no increase in the clinical efficacy of chloroquine was observed (P=0.05). In view of these results we propose more emphasis on information campaigns to increase public awareness of the need for chemoprophylaxis only for pregnant women, on the promotion of the use of bednets and insecticide-impregnated materials, and on environmental management.