Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T-cell proliferation and IL-2 production in response to synthetic peptides spanning the entire gp120 of HIV-1. At baseline, significant T-cell proliferative to pooled and individual peptides was observed in 15 of the 36 donors. After 12 months, proliferative responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T-cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL-2 production appeared to be a more sensitive and longer preserved parameter of T-helper cell function: at baseline the majority of donors with no T-cell proliferation produced IL-2 in response to pooled peptides. This response was not decreased significantly after 12 months. The overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gp120, but no pool or individual peptide was recognized by all responders. Functional T-cell responses were not statistically correlated to CD4+ cell percentile and absolute numbers.