OBJECTIVE To describe the natural history of vertically acquired human immunodeficiency virus (HIV) infection. METHODS This was a prospective follow-up study. METHODS Ten centers of the European Collaborative Study participated. METHODS One hundred twenty-four HIV-infected children were born to women known to be infected at or before the time of delivery since 1986. METHODS Deaths, acquired immunodeficiency syndrome (AIDS), and HIV-related symptoms and signs were assessed. RESULTS In this cohort, treatment before the onset of AIDS was not universal. Less than 10% of children were treated with Zidovudine or intravenous gamma globulin before 6 months of age, with a steady increase to about 40% after 3 years of life. An estimated 23% (95% confidence interval: 15% to 31%) of infected children develop AIDS before the age of 1 year, and nearly 40% (27% to 50%) by 4 years. Ten percent (5% to 16%) die before age 1 year and 28% (16% to 41%) before age 5 years. Twenty-four months after the AIDS diagnosis, an estimated 48% (36% to 70%) of the children are still alive. Although after the age of 1 year immunologic abnormalities became increasingly common, the proportion of infected children with significant HIV-related symptoms or signs declined. CONCLUSIONS The progression of disease in this cohort of vertically infected children was not as fast as previously suggested, even though treatment was not widespread. Although infected children have a high risk of developing some manifestation of HIV infection early in life, serious HIV-related symptoms became less frequent with increasing age. This has important implications for health planning and care provision.