The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (Sa(O2)), excessive erythrocytosis (EE, measured by the level of hematocrit (Hct)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMS(score)) were measured. Postmenopausal women had higher Hct (50.2 ± 4.04 vs. 47.4 ± 4.13%, P < 0.001), lower Sa(O2) (81.9 ± 4.12 vs. 84.7 ± 3.14%, P < 0.001) and PEFR values (489 ± 101 vs. 534 ± 90 l/min, P < 0.02), and slightly higher CMS(score) (19.1 ± 3.37 vs. 17.9 ± 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE - Hct >56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMS(score) (>21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.