Primary cultures derived from pre-cancerous and cancerous human colon tissue are essential for understanding normal and abnormal growth function in the large intestine. Here presented are (i) the methodology for routine establishment of primary cultures of normal, adenoma- and carcinoma-derived cells, and (ii) data for the apparently protective role of vitamin-D compounds in colon carcinogenesis. The steroid hormone 1,25-dihydroxyvitamin D3 and some non-hypercalcemic analogs reduce the high mitotic rate of adenoma cells to that of normal colonocytes. After vitamin-D treatment, tumor cells are less proliferative and differentiation is enhanced. Primary-colon-cancer cultures display a mosaic pattern of vitamin-D-receptor expression, at the mRNA level and at the protein level, with varying intensity of expression in positive cells. This suggests that, in human colorectal tumors in vivo, a large fraction of cells will respond to genomic action of vitamin-D compounds.