Preliminary rehydration of Hemoccult II slides increases slide sensitivity for blood and lowers the false-negative rate for colorectal cancer. To test the effect of this modification on the false-positive rate due to peroxidase-containing foods, 156 healthy young subjects crossed between diets of differing peroxidase content. Hemoccult II slides were prepared in duplicate for testing with and without rehydration. When developed without rehydration, only seven (0.4%) of 1856 slides were positive, the positive results occurring with challenge diets containing 250 g rare red meat. With preliminary rehydration, 53 (5.7%) of 926 slides were positive, in 26 (17%) of the 156 subjects on a challenge diet that included rare red meat and uncooked fruit and vegetables. Well-cooked red meat also gave positive tests, Diets excluding red meat but with large quantities of uncooked fruit and vegetables produced only five positive results in 314 rehydrated tests, in 3 of 53 subjects. On a strict low-peroxidase diet, two of 310 tests, in 2 of 52 subjects, were positive. Rehydration of Hemoccult slides and exclusion of red meat and certain other high-peroxidase foods should give optimal sensitivity and specificity for colorectal cancer detection. The effect of these conditions on yield of lesions and false-positive rates should be tested in screening programs.