Infections by Cunninghamella bertholletiae have been on the increase in recent years. However, little is known about this fungus and its infection. To clarify the pathogenicity of C. bertholletiae, we made a murine model, and to our knowledge, the first infectious model of this fungus. ICR mice pretreated with cortisone acetate and cyclophosphamide were inoculated intratracheally with 5 x 10(5) spores of C. bertholletiae. About half of the mice died by day 4 and 90% died by day 9. C. bertholletiae was cultured from the lungs, and the pathological analysis disclosed diffuse hyphal growth in the lungs, resulting in necrosis in the later stage. Angioinvasion with alveolar hemorrhage was extremely pronounced from the early stage, and this was the most characteristic feature of this infection. Treatment with amphotericin B showed only minimal improvement of survival, comparable to the poor result of this treatment in actual human cases. In fact, our model has many similarities to the actual human infection by C. bertholletiae, and will be useful for further investigations of this infection.