Objective: The most common etiology of infectious diarrhea in hospitalized patients isClostridium difficile. No single laboratory test yields a definitive diagnosis. Four methods were evaluated for their sensitivity and specificity in patients who had clinically definedC difficile-associated diarrhea.Methods: Clinical criteria forC difficile-associated diarrhea were defined. All adult in-hospital patients whose stools were tested forC difficilewere prospectively followed. Stools were examined with culture on a selective medium, a commercial cytotoxicity assay (cta), and two commercially available enzyme immunoassays (eias) for toxin A (Meridian) and toxin AB (cbc).Results: During the study period 235 stool specimens from 185 patients were tested. Fifty-one patients were positive forC difficileor its markers,ctawas most sensitive (80%), whereascbc-eiawas most specific (98%). Differences in the sensitivities ofctaand Meridian-eiawere minor (80% versus 73.3%) and they were equally specific (95.5%).Conclusions: The sensitivity and specificity ofeiafor toxin A is similar to other tests. However, due to rapidity and ease of performance, it may be a more practical test for the diagnosis ofC difficile-associated diarrhea, especially if the cytotoxin assay is not available.