The influence of sex steroid hormones on plasma calcitonin levels in healthy subjects was studied in 15 males and 10 premenopausal (PREMF) and 12 postmenopausal females (PMF). A standardized ionized calcium stimulus was achieved by means of the calcium clamp technique, and a sensitive RIA was used to determine immunoreactive CT (iCT) in plasma. Plasma iCT levels increased in response to the calcium clamp with an initial peak at 15 or 30 min. The iCT levels then declined but remained at an elevated level for the rest of the 180-min infusion period in all three groups. In males a positive correlation was found between the serum testosterone levels at 0 min and the estimates for initial iCT response, i.e., the change between 0 and 15 min (r = 0.80, n = 11, p less than 0.01), between 0 and 30 min (r = 0.56, n = 15, p less than 0.05) and between 0 and the maximum value (r = 0.68, n = 15, p less than 0.01). In the two female groups no such correlation was found. Serum 17 beta-estradiol or dehydroepiandrosterone sulfate concentrations were not correlated either to basal iCT levels or to the iCT response to the calcium clamp. PMF had lower levels of 17 beta-estradiol than PREMF (p less than 0.001), while the testosterone levels were similar. The iCT levels and response to the calcium clamp showed no significant difference in the two groups. The results indicate that sex difference in the plasma CT levels may be related to different testosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)