Nearly 40 million persons worldwide live permanently at elevation above 8,000 ft (2,439 m) and perhaps as great a number visit high-altitude regions annually. Health effects include the well-recognized altitude-specific syndromes of acute mountain sickness and high-altitude pulmonary edema. Emphasis is placed in this article on altitude-aggravated illness or those preexisting conditions that may be adversely affected by reduced O2 availability at high altitude. Examples from studies of pregnant women and their infants at high altitude are reviewed to demonstrate the effect of high altitude on maternal and fetal well-being. Increased maternal ventilation and ventilatory response to hypoxia during pregnancy at 10,200 ft (3,110 m) and 14,200 ft (4,329 m) raised arterial O2 saturation, helped to preserve arterial O2 content at levels present when nonpregnant, and correlated positively with the offspring's birth weight. Fetal growth retardation and an increased incidence of the complications of pre-eclampsia and neonatal hyperbilirubinemia at high altitude suggested that altitude may aggravate complications of pregnancy and prenatal life. Other conditions that may be aggravated at high altitude are reviewed. Virtually all studies on altitude-aggravated illness have been conducted on permanent residents. Future studies should seek to determine whether high altitude aggravates pre-existing conditions among the large and growing number of high-altitude visitors.