Sample size was calculated on the basis of a comparison of the three new drug regimens with the one used in the previous trial (SP + 1 dose of artesunate). It was assumed that about 20% of children in the SP + 1 dose of artesunate group would have Plasmodium falciparum parasitaemia at the end of the malaria transmission season providing around 100% samples for molecular studies. Assuming that the prevalence of resistance mutations at the dhfr codons 108, 59 and 51 was about 90%, 500 children would be needed in each study arm to give a trial with 90% power to detect a 20% reduction in the prevalence of resistance mutations in children receiving the new drug combinations at a 5% level of significance. Allowing for a loss to follow-up of about 10% a sample size of 2,200 was selected.