To determine the influence of neurologic manifestations of primary human immunodeficiency virus (HIV) infection on disease progression, 277 nonhemophiliac adults enrolled < 1 year after HIV infection were studied. Patients with neurologic manifestations during symptomatic primary HIV infection (PSI) (group N+; n = 23), with nonneurologic manifestations (group N-; n = 112) during PSI, and without any clinical manifestation during primary infection (group NPI; n = 142) were compared for disease progression. Age at infection, sex, mode of infection and CD4+ cell count at first visit did not differ between groups. In a Cox model, the relative risk (RR) of developing AIDS was 6.11 (95% confidence interval [CI], 1.94-19.28) in group N+ and 2.32 (95% CI, 0.93-5.83) in group N- compared with group NPI. The RR of AIDS onset after adjustment for treatment and age at infection was, respectively, 4.65 (95% CI, 1.43-15.03) and 2.03 (95% CI, 0.80-5.19) in groups N+ and N-. Neurologic manifestations of primary HIV infection are associated with an accelerated progression of disease.