We compared two Clostridium difficile latex agglutination tests, Meritec from Meridian Diagnostic (Cincinnati, Ohio) and CDT from Becton-Dickinson (Cockeysville, Md), on 289 specimens submitted for tissue culture cytotoxicity using MRC-5 cells. When compared with CDT, the Meritec latex agglutination test had a sensitivity of 90% (26/29), a specificity of 97% (251/260), and a correlation of 96%. Meritec was compared with tissue culture cytotoxicity on 357 specimens. Meritec had a sensitivity of 77% (30/39), a specificity of 93% (298/318), and a correlation of 92%. Clinical review of 10 Meritec +/- tissue culture cytotoxicity minus patients revealed one likely, two probable, and seven doubtful cases of C difficile disease. In contrast, review of 10 Meritec +/- tissue culture cytotoxicity plus patients showed seven likely and three probable cases of C difficile disease. The Meritec is comparable with the CDT latex agglutination test, but is not nearly as sensitive as either tissue culture assay or culture for detection of C difficile disease. A positive latex agglutination test should be confirmed by a tissue culture cytotoxicity assay.