Human immunodeficiency virus type 1 (HIV-1) circulates in vivo as heterogeneous mixed populations (quasispecies). We analyzed the quasispecies nature of the first, second, and third hypervariable loops (V1, V2, and V3) of the gp 120 in plasma and viral isolates obtained from 19 infected individuals. Sequence analysis of 7 SI and 10 NSI isolates showed that the increased positive charge in V3 and elongation of V1 clearly correlated with viral SI capability in PBMC. Contrary to the previous report (M. Groenink et al. Science 260: 1513-1525, 1993), there appeared to be no correlation between SI or non-SI phenotype and length of V2. However, all the 5 isolates with long V2 and basic V3 showed SI phenotype, whereas 4 out of 6 isolates with short V2 and basic V3 showed NSI phenotype, still suggesting some functional cooperation of V2 and V3 on viral syncytium inducing capability. Sequence analysis of HIV-1 in plasma showed the positive correlation between V3 charge and V1 or V2 length in 4 cases. This result suggests the associated evolution of V1/V2 and V3 in these cases.