The measurement of estrogen as well as progesterone receptors has been applied clinically to predict the effectiveness of endocrine therapy in patients with breast or endometrial carcinoma. The presence of cytosolic estrogen receptors in human colorectal carcinomas has been reported by several different groups during the past 10 yr. The aim of our current study was to evaluate the estrogen binding activity in the nuclear and cytosolic fractions of these carcinomas, as well as in surrounding noncancerous colonic tissue. Twenty-six patients, operated on for colorectal carcinoma, were studied: 16 were men and 10 were postmenopausal women, mean age 61 yr (range 43-78 yr). In neoplastic tissue, cytosolic estradiol receptors were detected in 42.3% of the patients (women 40%, men 43.7%). The values for cytosolic estrogen receptor ranged from 118 to 1214 fmol/g wet colon. Nuclear estrogen receptors were detectable in 46.1% of the patients (women 40%, men 50%) and their values displayed a range from 3.4 to 2554 fmol/g wet colon. In 30.7% of the patients, both nuclear and cytosolic receptors were demonstrated. In 38.4% of the patients, receptors were found in neither cytosol nor nuclei. Receptor positivity in men was most frequently associated with tumors removed from the rectum, and those with Dukes' classification of C1. In the surrounding noncancerous tissue cytosolic estrogen receptors were also detected (range 133-1105 fmol/g wet colon) and were present in 34.6% of the patients (women 30%, men 37.5%). Nuclear estrogen receptors (range 225-1105 fmol/g wet colon) were detected in 57.6% of the patients (women 40%, men 68.7%). In 23% of the patients, both nuclear and cytosolic receptors were demonstrated. In 30.7% of the patients, no receptors were found in either cytosol or nucleus. Therefore, the presence of cytosolic or nuclear estrogen receptors, or both, in 61.6% of human colorectal cancer specimens emphasizes the need to evaluate both forms of these receptors for studies of potential hormone dependence in these tumors.