In the last ten years microsporidia have been recognized as opportunistic pathogens in AIDS patients. The sources of infection and the mechanisms of transmission of these organisms in humans are mostly uncertain. Transmission of invertebrate microsporidia to mammals is normally considered impossible, temperature being a limiting factor for development. Mice treated with cortisone acetate and with cyclosporin A, respectively, as well as athymic nice were injected intravenously, intranasally, perorally and subcutaneously with spores of Nosema algerae, a microsporidian species of culicine mosquitoes. No infection could be detected in tissue samples of cortisone acetate and cyclosporin A treated mice. However, the experimental inoculation of spores into the tail and foot of athymic mice caused severe infection in skeletal muscles and the connective tissue. In some tails, nerve tissue and bone marrow were also infected. Vegetative stages and spores were seen in direct contact to host cell cytoplasma. For the first time the prolonged and progressive development of an invertebrate microsporidium in a mammalian host is shown. The possibility of invertebrate microsporidia as a source of human microsporidiosis should now be taken into consideration.