1 alpha,25-Dihydroxyvitamin D3, (1,25(OH)2D3), the active metabolite of vitamin D3, has important physiological effects on growth and differentiation in a variety of malignant and non-malignant cell types. In order to better understand the significance of 1,25(OH)2D3 receptors (VDR) in human colorectal cancer, we determined the levels of VDR in paired samples (malignant and adjacent normal tissues) of 24 colorectal cancer bearing patients. Our results demonstrated differences in the relative abundance of VDR between normal and transformed tissues according to the localization of the tumor. While colonic tumors exhibited significantly higher VDR values than their normal counterparts, the contrary seemed to occur in the rectal tumors. In colonic tumors, we found significant correlations between VDR levels and the absence of node involvement or a low Astler-Coller stage. The increased VDR values in colonic tumors as compared with the normal adjacent tissues, may warrant, at least in this type of cancer, the action of 1,25(OH)2D3 or its non-calcemic analogs, to help induce cell differentiation and growth inhibition.