The spread of HIV-1 to the nervous system occurs early during infection in a large number of asymptomatic virus carriers. In order to address the question whether the brain is targeted by a group of HIV-1 variants with increased neurotropic properties we have obtained 20 paired isolates from the blood and cerebrospinal fluid (CSF) of patients with varying severity of HIV-1 infection. We determined the nucleotide sequence of variable region 3 (V3) of the gp 120 envelope protein and studied the growth capacity of the virus isolates in primary monocyte/macrophage cultures. Blood and CSF V3 sequences could be grouped according to the host, whereas particular amino acid sequences related to tissue specificity were not identified. Moreover, the majority of HIV-1 isolates, independently of the tissue source, replicated in macrophage cultures. The isolates derived from the brain and blood compartments thus appeared genetically similar and could not be grouped according to their replicative capacities. The genetic distance between paired CSF and blood sequences was more pronounced in the group of patients with AIDS than in asymptomatic virus carriers. These observations indicate that the viruses present in the blood and CSF in the early stage of infection are genetically similar. Different mechanisms of adaptation or immunomodulation of the virus in CSF and blood may account for the increased intra-patient variability observed in the AIDS group.