Intracellular calcium [(Ca2+)i] was measured in human colonic epithelia derived from control mucosa from noncancer patients, from grossly "normal" mucosa taken 10-30 cm proximal to primary colorectal cancers, and from colorectal cancers. (Ca2+)i was measured first in cells bathed by calcium-free solution and again after adding 1 mM calcium. Compared to control mucosa, (Ca2+)i was 27% lower in cancer cells in the presence of 1 mM extracellular calcium, whereas (Ca2+)i was elevated more than 3-fold in the adjacent "normal" mucosa from cancer patients in both media. These results suggest altered (Ca2+)i levels in malignant cells and the presence of a "field defect" in (Ca2+)i regulation in "normal" colonic mucosa adjacent to colorectal cancers.