BACKGROUND: Madagascar was one of the first African countries to be affected by the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection. The outbreak started in the capital city, Antananarivo, and then spread throughout the country from October 2009 through February 2010. METHODS: Specimens from patients presenting with influenza-like illness were collected and shipped to the National Influenza Center in Madagascar for analyses, together with forms containing patient demographic and clinical information. RESULTS: Of the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and seasonal influenza virus, respectively. Most specimens (42.0%) received were collected from patients <10 years old. Patients <20 years old were more likely than patients >50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1; 95% confidence interval, 1.7-2.6; P < .01). Although phylogenetic analyses of A(H1N1)pdm09 suggested multiple introductions of the virus into Madagascar, no antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and those that circulated worldwide were observed. CONCLUSIONS: The high proportion of respiratory specimens positive for A(H1N1)pdm09 is consistent with a widespread transmission of the pandemic in Madagascar. The age distribution of cases of A(H1N1)pdm09 infection suggests that children and young adults could be targeted for interventions that aim to reduce transmission during an influenza pandemic.