Abstract. The clinical course of 37 Enterocytozoon bieneusi-infected acquired immunodeficiency syndrome patients with diarrhea was studied. Parasite clearance was seen in 15 patients (40.5%). Clearance of E. bieneusi resulted in a 25-100% reduction in episodes of diarrhea, suggesting that microsporidia are true pathogens. Univariate and multivariate proportional hazards analyses revealed that peripheral blood CD4 cell counts Ն 100/mm 3 , the use of two or more antiretroviral medications, and use of a protease inhibitor were statistically associated with decreased time to clearance of E. bieneusi. Specific anti-microsporidial therapy (albendazole) was not associated with parasite eradication. Factors related to immunocompetence and human immunodeficiency virus suppression appeared to be important in the clearance of E. bieneusi.The clinical entity of Enterocytozoon bieneusi-related diarrhea first characterized by Modigliani and others 1 and Desportes and others 2 was originally considered to be a relentless, progressive, wasting condition with significant morbidity and mortality seen in severely immunosuppressed patients with CD4 cell counts generally less than 100 cells/ mm 3 . 1-3 Parasite eradication using metronidazole, albendazole, and thalidomide was considered problematic. [4][5][6] Recent observations suggest that the clinical course of E. bieneusi-associated gastrointestinal infection has changed from its original description. A four-year evaluation of the yearly and seasonal prevalence of microsporidiosis in southern California by our group revealed a large, and statistically significant, decrease in yearly prevalence in 1995 and 1996 as compared to 1993 and 1994 (Conteas CN, OGW Berlin, unpublished data). Closer scrutiny of acquired immunodeficiency syndrome (AIDS) patients with E. bieneusi-associated diarrhea revealed patients with higher CD4 cell counts than previously considered to predispose to E. bieneusi infection. 7 Parenthetically, intact cellular immunity correlated well with spontaneous clearance (in the absence of antiprotozoal therapy) in two documented cases of self-limited E. bieneusi-related diarrhea in human immunodeficiency virus (HIV)-negative, nonimmunosuppressed individuals with normal cell-mediated immunity. 8,9 The goal of this study was to evaluate the clinical course of E. bieneusi-associated diarrhea with special attention directed to major factors related to immune competence; specifically, the status of the patient's cell mediated immunity and the number and types of antiretroviral drugs used.