The mechanisms involved in the antiproliferative action of calcitriol (1α,25(OH) 2 D 3 ) were investigated using human breast carcinoma epithelial cells (the MCF-7 cell line). Calcitriol and KH1060, a synthetic analog, inhibited cell growth in a time- and dose-dependent way. The substances similarly stimulated total TGF-β secretion after 24 hours, and Northern blot analyses showed that mRNA levels for TGF-β1 were increased, as well. When MCF-7 cells were co-incubated with calcitriol and a neutralizing antiTGF-β1,β2,β3 antibody, growth inhibition was completely abrogated. With KH1060, the antibody could only partly block growth inhibition. This study shows that TGF-β is involved in the growth response to calcitriol and KH1060 in MCF-7 cells.