Interferon gamma receptor knockout mice developed a chronic infection when inoculated with spores of Encephalitozoon intestinalis which is a cause of intestinal microsporidiosis in AIDS patients. The infection was evaluated by enumeration of the spores of the parasite shed in the stools, histological examination and follow up over a period of six months. A dose-response was demonstrated since higher numbers of spores were excreted and more infection sites were found in mice which were given an increased quantity of parasites. In infected wild type mice, the number of excreted spores decreased until day 16 post-inoculation, then spores were detected sporadically in low numbers. These data confirmed the role of IFN-gamma in the control of E. intestinalis infection. The infection was not lethal suggesting that other factors are involved in regulation of the parasite infection. This model, with the long survival time of the animals together with the measurable quantity of spores shed in the stools will be useful for testing potential therapeutical agents.