High-altitude is a physiological stress which induces hypertrophy of the erythropoietic marrow leading to deterioration of bone biomechanical competition (1). Lead (Pb) is a persistent air pollutant implicated in bone disorders (2). The increase in mining activities at high altitude frequently results in populations chronically intoxicated with Pb under hypoxic conditions. We reported growth retardation and damages on femoral bone that predispose to fractures in a rat model performed intoxicating the animals with Pb and exposing them to intermittent hypobaric hypoxia (IHH) (3). These findings aimed us to investigate the deleterious effect of Pb under IHH on bone biology, evaluating the intrinsic stiffness and the efficiency of spatial distribution of bone material to resist deformation, bone mass in terms of histomorphometry and some stress indicators. Sixty female Wistar growing rats were divided into: C (control); Pb (1000 ppm of lead acetate in drinking water for 90 d); IHH (exposed to 506 mbar, 18 h/d during 90 d in a simulated high altitude chamber) and PbIHH (both treatments together). After euthanasia, blood samples were collected to evaluate tumoral necrosis factor-alpha (TNFα); adrenal glands were resected and hemimandibles, femurs and tibiae were dissected to assess cortical mechanical properties (Instron 4442) and histomorphometric studies in decalcified sections stained with H&E. Values are means ± SD, compared by ANOVA and Student-Newman-Keuls. TNFα plasmatic concentration was greater in Pb and IHH animals (53.71±9.65 and 184.11±28.18 vs 2.91±0.78, p<0.01). Adrenal gland weight from Pb and IHH groups rose to similar levels (10.78±1.08 and 10.77±0.90 g/100g BW vs 7.99±1.00 for control rats, p<0.01) being the increase even greater for the PbIHH group. Stress, a bone material quality indicator, was reduced either by Pb or IHH in both kinds of bones (femur: Pb 90.36±8.91; IHH 59.95±4.89 and PbIHH 80.61±5.03 vs C 102.08±13.84 Nmm-2 and hemimandible: Pb 22.96±5.96; IHH 26.39±4.68 and PbIHH 24.69±3.92 vs C 39.25±8.50 Nmm-2, p<0.01). Treatments reduced only the hemimandible cross sectional geometry (Pb 3.78±0.67; IHH 4.13±0.51 and PbIHH 4.23±0.13 vs C 5.02±0.49 mm4, p<0.01) and the intrinsic stiffness (Pb 565.32±46.31; IHH 555.39±49.31 and PbIHH 526.31±45.31 vs C 796.32±59.36 Nmm-2, p<0.01). Combined treatments reduced tibia and hemimandible bone volume (-45 % and -40% respectively, p<0.01) and growth plate cartilage thickness (-19%). These results show a previously unreported effect of heavy metals under intermittent hypoxia on bone. Longer studies should be necessary to evaluate if an adaptation of the architecture to maintain structural properties may occur and if an association between the impairment of bone material quality and the degree of oxidative stress exists. UBACyT 20020090200013.