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<p>Abstract</p> <p>Background</p> <p>In view of the high level of chloroquine resistance in many countries, WHO has recommended the use of combination therapy with artemisinin derivatives in the treatment of uncomplicated malaria due to <it>Plasmodium falciparum</it>. Four antimalarial drug combinations, artesunate plus amodiaquine (Arsucam^®), artesunate plus mefloquine (Artequin^®), artemether plus lumefantrine (Coartem^®; four doses and six doses), and amodiaquine plus sulphadoxine-pyrimethamine, were studied in five health districts in Senegal.</p> <p>Methods</p> <p>This is a descriptive, analytical, open, randomized study to evaluate the efficacy and tolerability of these four antimalarial combinations in the treatment of uncomplicated falciparum malaria using the 2002 WHO protocol.</p> <p>Results</p> <p>All drug combinations demonstrated good efficacy. On day 28, all combinations resulted in an excellent clinical and parasitological response rate of 100% after correction for PCR results, except for the four-dose artemether-lumefantrine regimen (96.4%). Follow-up of approximately 10% of each treatment group on day 42 demonstrated an efficacy of 100%.</p> <p>The combinations were well tolerated clinically and biologically. No unexpected side-effect was observed and all side-effects disappeared at the end of treatment. No serious side-effect requiring premature termination of treatment was observed.</p> <p>Conclusion</p> <p>The four combinations are effective and well-tolerated.</p>