OBJECTIVE To study the association between placental morphology and full-term birth weight at high and low altitude. METHODS Twenty normal pregnant women living permanently at high altitude (3100 m) and 20 normal pregnant women living permanently at low altitude (500 m) in Southern Saudi Arabia. METHODS For each subject in the two groups the mean hemoglobin concentration and hematocrit values throughout pregnancy were estimated and these were used as indices for maternal hypoxia. After delivery, the birth weight of each fetus was determined together with the placental weight. Placentas were then examined histologically using sections stained by periodic acid-Schiff and hematoxylin-eosin. The mean percentages of villi with syncytial knots, cytotrophoblastic cells and fetal capillaries were determined. RESULTS The mean hemoglobin concentration and hematocrit values were significantly greater at high altitude than at low altitude (P < 0.001 for both). The mean birth weight and placental weight were significantly greater at low altitude compared to high altitude (P < 0.025 and 0.001, respectively). The placentas from high altitude showed histological changes suggestive of placental hypoxia i.e. significant increase in the incidence of syncytial knots, cytotrophoblastic cells and fetal capillaries at high altitude compared to low altitude (P < 0.005, 0.001 and < 0.05, respectively). At both high and low altitude the incidences of syncytial knots and cytotrophoblastic cells showed positive and significant correlations with mean maternal hemoglobin (r = 0.5 and 0.6, P < 0.01 and < 0.001, respectively) and hematocrit (r = 0.5 and 0.6, P < 0.01 and 0.001, respectively) during pregnancy and negative and significant correlations with fetal birth weight (r = -0.4 and -0.6, P < 0.01 and P < 0.001, respectively). CONCLUSIONS The low birth weight observed at high altitude compared to low altitude appeared to be mainly secondary to placental hypoxia resulting from maternal hypoxia which in turn was caused by high altitude hypoxia.