In countries of the Sahel and sub-Sahel, malaria transmission is highly seasonal with nearly all episodes of malaria occuring during a few months of the year. However, mortality and morbidity from malaria may be very high during this period, especially in children who are the most vulnerable group. It has been shown previously in The Gambia and elsewhere in West Africa that regular administration of anti-malarial drugs throughout the period of malaria transmission (chemoprophylaxis) reduces mortality and morbidity substantially but chemoprophylaxis is difficult to sustain. Intermittent preventive treatment (IPT) differs from chemoprophylaxis in that drugs are given at less frequent intervals and drug concentrations fall below the inhibitory level between administrations. IPT was used first to protect pregnant women from malaria and this approach has proved very effective. More recently, the IPT concept has been applied to the prevention of malaria in infants, drugs being given at the same time as infant vaccines are administered. However, in areas of seasonal malaria, such as Senegal, only a small proportion of cases of severe malaria occur during the first year of life. In such areas, older children require protection. Intermittent preventive treatment in children (IPTc) is a potential way of doing this. IPTc involves the administration of drugs to all children in the age group at risk on two or three occasions during the period of high malaria transmission. In a recent study in Senegal it was shown that the administration of a single dose of sulfadoxine/pyrimethamine (SP) plus artesunate to children aged 6 weeks to 59 months reduced the incidence of clinical attacks of malaria by 86%. However, administration of these drugs was associated with selection of parasites with molecular markers of resistance to pyrimethamine and to sulfonamides. The aim of the new study was to investigate alternative drug regimens which might be equally effective but less likely to select for drug resistance.