Weight loss is a common characteristic of advanced stages of HIV infection. Weight changes during the asymptomatic stage of HIV infection have not been well documented and the possible predictive value of early weight loss for progression to AIDS is unknown. In 122 HIV seroconverters, the natural course of body mass index (BMI) following seroconversion was studied. No BMI decline was seen immediately following seroconversion. In the 56 AIDS cases, however, a steep BMI decline of 1.14 kg/m2 occurred 6 months before AIDS. This BMI decline was more pronounced in those with low CD4+ T cell counts (<100 × 106/L) at the time of AIDS diagnosis (1.8 kg/m2). The relative hazard for progression to AIDS of a BMI decline of 1.14 kg/m2 per 6 months was 3.1, which remained similar after adjustment for CD4 count and p24 antigenemia. We conclude that the course of BMI in HIV-1 infection is biphasic: a relatively stable period is followed by a rapid decline in the 6 months preceding onset of AIDS. Furthermore, we found that this steep BMI decline was associated with faster progression to AIDS.