Ageing, independently from the hormonal status, is a major risk factor for cardiovascular morbidity in healthy women. Therefore, we studied the effect of healthy ageing on the cardiovascular homeostatic mechanisms in premenopausal and postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal women, confirmed by FSH and LH levels, were compared to 14 normally menstruating women during the early follicular phase (young-EF), in order to avoid as much as possible the effects of estrogen. Systolic BP was 108±1.5 vs. 123±2.5 (p<0.001), supine norepinephrine was 260±30 vs. 216±45 and upright 640±100 vs. 395±50 pg/ml (p=0.05) in young-EF vs. postmenopausal, respectively. Plasma renin activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased significantly with ageing (young-EF vs. postmenopausal): Hf band, rMSSD and PNN50% were 620±140 vs. 270±70 (p=0.04), 53±7 vs. 30±3 (p=0.02), and 23±5 vs. 10±3 (p=0.04), respectively. Lf to Hf ratio was 0.85±0.17 in young-EF and became 1.5±0.22 in postmenopausal (p=0.03). Both arms of the baroreflex, +BRS (29±5 vs. 13.5±2.5, p=0.01) and -BRS (26±4 vs. 15±1.5, p=0.02) decreased with ageing. Cardiovascular 1-adrenoreceptor responsiveness significantly increased and -decreased, in postmenopausal compared to young-EF (p<0.001, both). The QTc intervals were similar, whereas JTc and JTc to QTc ratio were prolonged in the postmenopausal group. We conclude that in young women, parasympathetic control is the main regulator of the cardiovascular system and in postmenopausal women sympathetic tone dominants. The transition from parasympathetic to sympathetic control may contribute to the increased cardiovascular morbidity with ageing.