To further understand the pathological characteristics of multiple organ involvement of the 2009 pandemic influenza A/H1N1 infection, tissues of bronchial mucosa, lung, myocardium, gastrocnemius, and liver from 3 patients with fatal A/H1N1 infections were investigated by light microscopy and transmission electron microscopy. In all 3 patients, bronchial mucosa showed necrotizing bronchiolitis, epithelial necrosis and desquamation, and squamous metaplasia, while lung consolidation or fibrosis was identified. Myocardium and gastrocnemius exhibited focal necrosis and fibrosis, surrounded by muscle cells showing features of cell damage. In liver, there was widespread fatty degeneration and necrosis, most often around the central lobular vein and portal area. Viral particles were found in all samples, frequently located in endothelium, epithelium, and muscle cells. The observations demonstrate that in fatal cases of A/H1N1 infection, viruses not only infect the respiratory system, but also engage in multiple organ invasions, causing pathologic changes.