To determine their diagnostic utility, fecal leukocytes were sought by methylene blue stain in 502 consecutive stool specimens submitted for Clostridium difficile toxin assay. In addition, the stability of fecal leukocytes was assessed by daily examination of 23 stool specimens stored at 4 degrees C and room temperature. The sensitivity, specificity, and positive and negative predictive values of fecal leukocytes in predicting C. difficile toxin assay results were 28%, 92%, 27%, and 93%, respectively. At 4 degrees C, fecal leukocytes retained morphology for a minimum of 3 days. Leukocytes survived as long in stool specimens containing either C. difficile toxin or an enteric pathogen as they did in stool specimens with neither finding. We conclude that testing stool specimens for fecal leukocytes is not useful for predicting the presence of C. difficile toxin, because 72% of stool specimens positive for C. difficile toxin are negative for fecal leukocytes despite their stability.