To determine whether oral iron preparations taken in therapeutic doses are capable of causing either true-positive, false-positive, or false-negative fecal occult blood Hemoccult tests, a prospective, before/after trial was conducted in the gastroenterology clinic of an Army medical center. Fourteen healthy volunteers were studied in four 1-wk periods, during which a single stool sample was collected on the 3rd, 5th, and 7th days for Hemoccult testing and HemoQuant assay. No iron preparations were ingested during the 1st and 3rd wk, and these results served as control values. One 324-mg tablet of ferrous sulfate was ingested orally three times each day during the 2nd wk and one 324-mg tablet of ferrous gluconate was ingested three times each day during the 4th wk of the study. All 84 stool specimens collected during the 2 wk of oral iron therapy were negative on Hemoccult testing, and the results of corresponding quantitative assays for fecal blood by the HemoQuant method were normal and did not differ significantly from control values. The Hemoccult test results from our study differ markedly from those of a previous study of similar design using only Hemoccult tests and oral iron preparations. Also, our HemoQuant data confirmed that oral iron preparations, in therapeutic doses, do not interfere with HemoQuant assay. Ferrous sulfate and ferrous gluconate tablets ingested in therapeutic doses do not cause false-positive, true-positive, or false-negative stool Hemoccult tests and do not cause a significant increase in gastrointestinal blood loss compared to controls as assessed by the Hemo-Quant assay. Any positive stool Hemoccult test detected in individuals ingesting therapeutic doses of oral iron preparations should not be regarded as a false-positive test.