In order to examine the relevance of early immune activation to the long-term course of HIV infection, we evaluated the ability of the serum beta 2-microglobulin level measured in 63 haemophiliacs on average 4.9 months from HIV seroconversion to predict the rate of development of server immunodeficiency (CD4) lymphocyte count 50/mm3) or AIDS over the following 10 years. Patients with higher beta 2-microglobulin values tended to develop severe immunodeficiency/AIDS more rapidly than those with lower levels (relative risk 1.68 per 1 mg/L increase; 95% CI 1.26-2.26; p = 0.0004). Older patients also progressed more rapidly, and these two factors acted independently (relative risk 1.65 per 1 mg/L increase; 95% CI 1.21-2.72; p = 0.002 for beta 2-microglobulin and 1.22 per 10 years; 95% CI 1.01-1.48; p = 0.04 for age). These results provide further evidence that the long-term course of HIV infection can, to some extent, be predicted soon after infection. Older patients with high beta 2-microglobulin levels warrant close monitoring and consideration for early antiretroviral therapy.