We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.