Recently there have been several reports documenting the presence of estrogen receptors (ERs) in human gastrointestinal (GI) malignancies, raising the possibility that these cancers may be hormonally manipulated. To test this hypothesis, 68 frozen GI tissue specimens were examined for the presence of ERs within the cell nuclei by immunohistochemical staining. There were 51 cancers (25 gastric, 26 colon) and 17 normal tissue specimens (six gastric, 11 colon). Tissue sections 4 to 6 microns thick were incubated with monoclonal antibody H222SP psi, then stained by the peroxidase-antiperoxidase technique for visualization of the ER. The staining was semiquantitatively graded from 0 to 3+ depending on both the intensity of staining and the percentage of cell nuclei stained. A breast cancer specimen known to be strongly positive for the ER was used as a positive control. The 30 male and 21 female cancer patients had a median age of 59 years. All tumors were adenocarcinomas. Eight per cent of the gastric cancers were poorly differentiated, while 94 per cent of the colon cancers were moderately well to well differentiated. Using weak staining of at least 20 per cent of the cell nuclei as the minimum requirement for an ER positive tumor (1+, 0/51 tumors and 0/17) normal specimens were positive for ER. Only three out of 25 (12%) gastric tumors, and two out of 26 (8%) colon tumors demonstrated any staining; each exhibited weak staining of only five to ten per cent of the tumor nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)