We sought to determine if any protective effect of dietary calcium (Ca) or Ca supplements on bone could be at least partially mediated by increased calcitonin (CT) secretion. First we studied 10 healthy premenopausal women (median age, 35.5 years) who were randomized to high or low dietary Ca intake (1752 versus 391 mg elemental Ca per day) for 2 weeks and then crossed over. At the end of each dietary period, blood was drawn on 1 day at 0800, 1200, 1700, and 2000 h to assess diurnal variation of plasma CT levels. CT secretory reserve was assessed on the next day by Ca infusion (2 mg Ca per kg body weight over 5 minutes). Next, we studied 10 healthy premenopausal women who took a low-Ca diet (approximately 400 mg Ca per day) for a 2 week control period. The women were then randomized to high- or low-Ca intake [400 mg dietary Ca +/- 1500 mg Ca per day (as supplemental CaCO3)] and then crossed over. At the end of each study period, the diurnal variation in CT was tested on day 1; the CT secretory reserve was assessed on day 3 by an oral Ca load (500 mg as CaCO3)] and on day 5 by Ca infusion. Plasma immunoreactive CT was measured in whole plasma (iCT) and after silica extraction (exCT), predominantly monomeric CT. Neither increased dietary Ca nor Ca supplements affected the diurnal levels of iCT or exCT or augmented plasma CT responses to an oral Ca load.(ABSTRACT TRUNCATED AT 250 WORDS)