Objective. To compare fecal screening tests in the diagnostic approach to childhood invasive diarrhea. Setting and patients. We assessed 125 consecutive children with acute diarrhea for fecal lactoferrin, fecal leukocytes and occult blood from November, 1995, to June, 1996. Results. Lactoferrin showed a greater overall sensitivity than fecal leukocytes or occult blood for detecting invasive pathogens. Combinations of lactoferrin or fecal leukocytes and of actoferrin or occult blood or both yielded sen- sitivities and negative predictive values close to 100%, being superior to all other combinations. All patients with full breast-feeding and mixed feeding had a positive lactoferrin test with a 1:50 dilution used as the cutoff. In controls without diarrhea being exclusively bottle-fed, 3 of 15 (20%) still showed a positive lactoferrin result at the dilution of 1:50. This compared with 15 of 15 (100%) positive results among controls fully breast-fed, 14 of 15 (93%) among controls predominantly breast-fed and 11 of 15 (73%) among control children predominantly bottle-fed. Conclusions. This study confirms the usefulness of lactoferrin testing as a negative predictor. Breast-feeding lowers the specificity of the test but does not alter the sensitivity. Fecal lactoferrin may be viewed as the screening test of choice to avoid expensive stool cultures in the diagnostic approach to invasive diarrhea.