This study was carried out in order to determine interrelationships of age and sex on parameters within the parathyroid endocrine system in healthy men and women. One hundred and fifteen normal subjects (70 females and 45 males) subdivided into three groups aged 25-35, 45-55 and 65-75 years were studied. Female subjects aged between 45 and 55 were further subdivided into two age-matched groups in relation to gonadal functional status. Serum intact parathyroid hormone (PTH) concentrations were measured using a two-site immunoradiometric assay. We found that there was a significant decrease of serum ionized calcium with ageing only in men (r = -0.666, P < 0.001) and a significant increase of serum PTH with age in both men (r = 0.488, P < 0.001) and women (r = 0.279, P < 0.019). A significant inverse correlation was found between serum ionized calcium and PTH in male subjects (r = -0.661, P < 0.001) and in fertile females (r = -0.353, P < 0.037) but not in postmenopausal women or in the entire female population. Furthermore, we found a significant decline of serum phosphate (r = -0.484, P < 0.001) and TmP/GFR (r = -0.492, P < 0.001) with advancing age in men, but not in women. We believe that the decrease of serum ionized calcium, as a likely consequence of the physiological reduction of intestinal calcium absorption, is the pivotal factor responsible for the increased PTH levels we observed with advancing age. The phenomenon is clear in men and in premenopausal women, but is masked in the female sex at menopause by the effects of a shortage of oestrogen on the calcium-phosphorus metabolism. These may also be responsible for the differences observed between the two sexes as far as phosphate metabolism is concerned. In conclusion, this study has, for the first time, taken relationships between serum ionized calcium and PTH, over a wide age range, into consideration. The results obtained show a marked difference of serum ionized calcium values between sexes with ageing, while serum parathyroid hormone levels increase in both men and women. Important differences also exist, as far as phosphate metabolism is concerned, between males and females.