BACKGROUND: Adverse environmental events occurring early in life have received little attention as predictors of disease in the later stages of life. At birth, the transition from gas exchange by the placenta to gas exchange by the lungs requires dramatic changes in the pulmonary circulation, which during this period is particularly vulnerable to noxious stimuli. We measured pulmonary-artery pressure responses to high-altitude exposure, a stimulus that causes pronounced pulmonary vasoconstriction, in young adults who had had transient perinatal hypoxic pulmonary hypertension and in controls of similar age and sex distribution. METHODS: Review of neonatal-care records at the Lausanne University Hospital for Children identified 15 individuals who met the eligibility criteria (birth at > or = 34 weeks of gestation, persistence of hypoxaemia during ventilation with oxygen during the first week of life, and persistence of fetal circulation). Ten of these individuals agreed to take part; the control group was ten volunteers without any history of perinatal complications. Systolic pulmonary-artery pressure (by echocardiography) and arterial oxygen saturation were measured at baseline and at high altitude (4559 m). FINDINGS: The mean increase in pulmonary-artery pressure at high altitude was significantly greater (p=0.01) in the participants who had had perinatal pulmonary hypertension (from 26.2 mm Hg [SD 2.1] to 62.3 mm Hg [7.3]) than in the controls (from 25.8 mm Hg [2.3] to 49.7 mm Hg [11.3]). The fall in arterial oxygen saturation was similar in the two groups. INTERPRETATION: These findings suggest that a transient perinatal insult to the pulmonary circulation leaves a persistent and potentially fatal imprint, which when activated in adult life predisposes to a pathological response. Survivors of perinatal pulmonary hypertension may be at risk of developing this disorder in later life.