Cytochrome P450 (CYP) 2C8 is the major enzyme responsible for the metabolism of many clinically important drugs including the antimalarial amodiaquine (AQ). This study investigated in 91 malaria-infected patients from Guinea-Bissau, the prevalence of CYP2C8 variants CYP2C8*2, CYP2C8*3 and CYP2C8*4, which may have important clinical implications for the efficacy and toxicity of amodiaquine. CYP2C8*2 and CYP2C8*3 alleles were found to be present in high frequencies in this population at 24% and 32%, respectively. Most of the subjects analysed were carriers of at least one variant allele. This suggests the possibility of a high occurrence of CYP2C8 poor metabolizer individuals among malaria patients in Guinea-Bissau, who may therefore be at a greater risk of adverse effects compared to other populations previously characterized.