OBJECTIVE The mechanism underlying the slight hypoandrogenism associated with normal ageing remains unclear. We have therefore examined age related changes in the activity of the pituitary-testicular axis In healthy normal males. DESIGN Random blood samples were obtained from 219 normal men whose ages ranged from 20 to 79 years. At the time of the study, none of the men had received treatment or had ever had any endocrine dysfunction diagnosed. MEASUREMENTS Luteinizing hormone was measured In the subjects' plasma using a commercially available immunoradiometric assay (IRMA, Serono Malaclone) and a fully validated In-vitro bioassay. Testosterone and FSH were measured using standard radioimmunoassays (RIA) whilst sex hormone binding globulin was assayed by an IRMA. RESULTS Levels of total testosterone (total-T) and bioactive LH fell with age (r=−0.231 and −0.189 respectively) by 5.9nmol/l and 2.3IU/I respectively between grouped patients aged 20-39 years (Group A) and 60–79 years (Group C). In contrast, immunoreactlve LH remained unchanged. The LH B:I ratio also fell with age (P<0.0001) being 5.0±0.3 (group A) and 3.3±0.2 (group C), representing a fall of 33%. Since Immunoreactivlty remained constant, this fall primarily represented the decline in LH bioactivity. Bioactive, but not immunoreactlve LH correlated to total-T (P=0.009, n=209) and the total-T:LH ratios fell by over 30% between groups A and C using the IRMA, but remained unchanged by bioassay. CONCLUSIONS There Is an underlying decline In both total-testosterone and free-testosterone index, and bioactive LH levels with advancing age, suggestive of a hypothalamo-pituitary defect which leads to lower bioactive LH levels which in turn are responsible for the diminished gonadal steroidogenesis. Elucidation of the mechanism underlying this slight decline in hypothalamo-pituitary testicular activity Is complicated by differences between the data obtained by immunoassay or bioassay.