Here we compare the results of pathological and virological examinations of mice experimentally infected with either wild-type or mouse-adapted pandemic A(H1N1) pdm09 viruses and highly pathogenic avian influenza (HPAI) virus A(H5N1). Mice were sacrificed on days 1, 3, 6, and 10 post infection or whenever morbidity was severe enough to justify euthanasia. Morbidity rates were calculated on the basis of clinical signs (weight loss, poor hair coat, hunched posture and paresis); virus-induced disease was characterised by the histopathology of lung; virus dissemination was determined by virus isolation on organ samples of lung, brain, liver, kidney and spleen. All mice infected with mouse-adapted A(H1N1) pdm09 died in the course of the experiment, whereas 20% of animals survived the infection with A(H5N1). Echinocyte formation changed the rheological properties of blood in animals infected with either mouse-adapted A(H1N1) pdm09 or A(H5N1). To sum up, the adaptation of pandemic A(H1N1) pdm09 virus can confer an enhanced virulence similar to or even exceeding that of HPAI A(H5N1) virus.