To carry out, within France, a large-scale molecular epidemiological investigation on the principal neutralizing determinant of HIV-1, located in the third variable region (V3) of the envelope protein. Such investigations are of the utmost importance in the identification and monitoring of the distribution and spread of different viral strains internationally. Using polymerase chain reaction (PCR), we examined the genetic variation of the V3 region sequences of 28 HIV-infected patients from Paris, France. Comparison of the Parisian V3 loop sequences with other published data indicates that the range of diversity in France is included within that of a large group that contains sequences from North America, the rest of Europe, Japan, India and Africa. Variability appears to be lower in the V3 loop than in its flanking regions. Five out of the six putative N-linked glycosylation sites show preferential alterations to charged amino acids. We report two motifs at the tip of the loop that have not been described previously. The structural homogeneity and the wide geographic representation of the major V3 group suggests that a common strategy could be applied to a large proportion of isolates in the development of a broad-spectrum HIV vaccine.