OBJECTIVE: Determine effects of raloxifene hydrochloride, a selective estrogen receptor modulator (SERM), on growth and proliferation of an estrogen-responsive endometrial cancer cell line in vitro. MATERIALS AND METHODS: Studies were performed with Ishikawa endometrial adenocarcinoma cells, a well-differentiated cancer that expresses estrogen receptors and progesterone receptors. Raloxifene was purified as the hydrochloride salt. The four arms of the study were cells grown (1) without any further addition (control), (2) with estradiol only, (3) with raloxifene only, or (4) with estradiol and raloxifene. Three concentrations of estradiol (10, 100, 1000 pg/ml) and raloxifene (1, 10, 100 ng/ml) were used. After 1 week of culturing, the number of living cells for each experimental group was determined and expressed as a percentage of the control group. RESULTS: Cells treated with raloxifene 10 or 100 ng/ml alone grew significantly faster than control cells: 10 ng/ml [115.25%; SD, 11.05; 95% confidence interval (CI), 107.35-123.16; P = 0.002] and 100 ng/ml (111.14%; SD, 14.19; 95% CI, 100.98-121.29; P = 0.03). Estradiol 10 or 100 pg/ml did not stimulate cell growth, whereas cells treated with 1000 pg/ml grew significantly faster than control cells (114.69%; SD, 16.84; 95% CI, 102.65-126.74; P = 0.02). Raloxifene and estradiol together in any concentration did not affect cell growth. CONCLUSIONS: Raloxifene did not inhibit the growth of endometrial cancer cells in vitro. High concentrations even promoted cell growth. Estradiol in physiologic concentrations did not stimulate the growth of endometrial cancer cells in vitro.