In a comprehensive search for T-cell epitopes of HIV-1, several new regions were discovered. The analysis was performed with lymphocytes of HIV-1-infected persons in various stages of the infection. Peptides covering the entire group antigen (gag), and transmembrane (gp41) regions, and one-half of envelope (gpl20) regions of HTL V-III B were studied. Both common and patient-unique responses were identified. Twelve common gag T-cell sites were discovered, as well as patient-unique activating peptides. The gag peptides elicited the most frequent cell responses and the responses remained in late stages of disease. Only 1 of the 12 T-cell activating gag peptides was reactive with specific anti-HIV IgG. Eighteen common env-representing peptides evoked T-cell responses. They could be grouped into four previously undescribed regions of gp120 and two known sites, the hypervariable stretch and part of the CD4 binding region. Cell responses to env peptides were common in early stages of disease and tended to decrease in ARC and AIDS. The gp41-representing peptides evoked a cellular response to a region close to the N-terminus of the hydrophobic transmembrane region. In addition to the T-cell activating peptides, peptides representing pl5 and pl9 as well as previously recognized regions of gp120 and gp41 appeared to be potent B-cell epitopes.