OBJECTIVE: To estimate the cost-effectiveness of malaria intermittent preventive treatment in infants (IPTi) using sulfadoxine-pyrimethamine (SP). METHODS: In two previous IPTi trials in Ifakara (United Republic of Tanzania) and Manhiça (Mozambique), SP was administered three times to infants before 9 months of age through the Expanded Programme on Immunization. Based on the efficacy results of the intervention and on malaria incidence in the target population, an estimate was made of the number of clinical malaria episodes prevented. This number and an assumed case-fatality rate of 1.57% were used, in turn, to estimate the number of disability-adjusted life years (DALY) averted and the number of deaths averted. The cost of the intervention, including start-up and recurrent costs, was then assessed on the basis of these figures. FINDINGS: The cost per clinical episode of malaria averted was US$ 1.57 (range: US$ 0.8-4.0) in Ifakara and US$ 4.73 (range: US$ 1.7-30.3) in Manhiça; the cost per DALY averted was US$ 3.7 (range: US$ 1.6-12.2) in Ifakara and US$ 11.2 (range: US$ 3.6-92.0) in Manhiça; and the cost per death averted was US$ 100.2 (range: US$ 43.0-330.9) in Ifakara and US$ 301.1 (range: US$ 95.6-2498.4) in Manhiça. CONCLUSION: From the health system and societal perspectives, IPTi with SP is expected to produce health improvements in a cost-effective way. From an economic perspective, it offers good value for money for public health programmes.