Although human immunodeficiency virus type 1 (HIV-1) specific CD4 T-helper cells are vital in mediating antiviral defence, little is known concerning the influence of HIV-1 antigenic variation on CD4 T-cell responses. In this study, the amino acid sequences of 5 synthetic HIV-1 envelope peptides used for in vitro stimulation (T2, P18 MN, P18 IIIB, T1 and TH4.1) were compared to the corresponding amino acid sequences of the gp 160 region of viruses isolated from HIV-1 infected children to determine whether variation in the envelope region of HIV-1 was associated with the ability to detect Env-specific T-helper cell responses. Although the T2 region appeared to offer some evidence as to the role antigenic variation may have played in class II-restricted CD4 T-cell responses between those children who showed a detectable Env-stimulated T-helper cell response and those who did not, the other regions studied showed no evidence of being more conserved among those children who showed detectable responses. The combined amino acid variation across the specific peptide regions studied was not associated with peripheral levels of HIV-1, nor did the degree of amino acid variation dictate the clinical category into which the children had been classified, although there was a tendency towards HIV-1 isolates from the younger children showing a greater degree of amino acid variation than isolates from the older children. These results suggest that HIV-1 specific CD4 responses may be somewhat tolerant of viral variation, although further studies are required to fully elucidate the effect of antigenic variation on immune recognition.