LoVo, a cultured colon cancer cell line, is shown to possess a receptor for 1,25-dihydroxy vitamin D3 (1 alpha,25(OH)2D3) with a low capacity (28 fmol/mg protein) and high affinity (Kd: 1.9 x 10(-21)0M). When these cells were grown in monolayer culture in a chemically defined serum-free medium, a significant inhibition of proliferation was seen in the presence of 10 nM to 1 microM of 1 alpha,25(OH)2D3 (p less than 0.005. Furthermore, 1 alpha,25(OH)2D3 delayed early attachment of cells. After 8 days of treatment, aggregated cuboidal cells showed a marked change to an apparently spindle like morphology. The 1 alpha,25(OH)2D3 growth-inhibitory effect was modulated by verapamil (1 microM), a calcium channel blocker, hydrocortisone (1 microM), and moxestrol (1 mM), an estrogen analogue, and 2% charcoal-treated fetal bovine serum. This study represents the first demonstration of 1 alpha,25(OH)2D3 modulation of growth of human colon cells.