Summaryobjective To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malariarelated morbidity in children <5 years of age who already had access to home-based management of malaria (HMM) for presumptive treatment of fevers.method Thirty community-based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunateamodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross-sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children.results During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: )9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2-78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration.conclusion In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.