The MODOR 1 trial randomised children younger than 5 years in communities in Niger, Tanzania, and Malawi to receive twice yearly mass treatment with oral azithromycin or placebo. All-cause mortality over 2 years, the primary outcome, was 13·5% (95% CI 6·7–19·8) lower in children in communities that received azithromycin compared with those that received placebo. These promising findings raise questions about the setting in which the intervention might be applied, and ethical issues concerning the potential effect of mass drug administration on development of antibiotic resistance.