We prospectively evaluate the value of fecal blood and fecal leukocytes in predicting whether acute diarrhea in adults is associated with a stool culture positive for a bacterial pathogen. One hundred thirteen patients, aged 19 to 50 years, seen in a two-year period in an urban adult outpatient setting underwent stool culture for the presenting symptom of diarrhea. Heterosexual men represented 48% of the cohort, women represented 17%, and homosexual men represented 35%. Overall, 53 (47%) of the patients had positive stool cultures for enteric pathogens. Campylobacter jejuni was the most common organism in the entire cohort, but Shigella species were most common in homosexual men. The best predictive variables for a stool culture positive for a bacterial pathogen were the presence of both fecal leukocytes and fecal blood in the stool, compared with only one or neither. When both were present, the sensitivity was 81%, the specificity 74%, and the predictive values of a positive and negative test were 81% and 83%, respectively; the likelihood ratio was 4.87. When homosexual men and the rest of the cohort were analyzed separately, the combination of fecal leukocytes and fecal blood remained the best method of predicting a positive stool culture in both. Examination of stool for fecal leukocytes and fecal blood is a rapid, reliable, and inexpensive way to differentiate between bacterial and other causes of acute diarrhea in the adult acute care setting.