BACKGROUND: Although there are many methods available for measuring compliance, there is no formal gold standard. Different techniques used to measure compliance were compared among children treated by the anti-malarial amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) combination therapy, in use in Senegal between 2004 and 2006. METHODS: The study was carried out in 2004, in five health centres located in the Thies region (Senegal). Children who had AQ/SP prescribed for three and one day respectively at the health centre were recruited. The day following the theoretical last intake of AQ, venous blood, and urine samples were collected for anti-malarial drugs dosage. Caregivers and children above five years were interviewed concerning children's drug intake. RESULTS: Among the children, 64.7% adhered to 80% of the prescribed dose and only 37.7% were strict full adherent to the prescription. There was 72.7% agreement between self-reported data and blood drug dosage for amodiaquine treatment. Concerning SP, results found that blood dosages were 91.4% concordant with urine tests and 90% with self-reported data based on questionnaires. CONCLUSION: Self-reported data could provide useful quantitative information on drug intake and administration. Under strict methodological conditions this method, easy to implement, can be used to describe patients' behaviors and their use of new anti-malarial treatment. Self-reported data is a major tool for assessing compliance in resource poor countries. Blood and urine drug dosages provide qualitative results that confirm any drug intake. Urine assays for SP could be useful to obtain public health data, for example on chemoprophylaxis among pregnant women.