The effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 +/- 2 years of age, mean +/- SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 +/- 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 +/- 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 +/- 2 pg/ml to 42 +/- 7 pg/ml, P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 +/- 0.2 mg/dl to 8.7 +/- 0.1 mg/dl, P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion.