The cytotoxic T lymphocyte (CTL) response has recently been shown to play a role in protection against human immunodeficiency virus (HIV) and it is therefore thought that a vaccine against HIV must be able to elicit a CTL response. The development of a safe, effective adjuvant is very important because alum, the only adjuvant available for use in humans at present, can barely induce a response of this type. We demonstrate here that liposomes that contain an immunodominant peptide (15 amino acids) of the envelope glycoprotein gp120 of HIV-1 and that are coated with mannopentaose-dipalmitoylphosphatidylethanolamine conjugate induce a major histocompatibility complex class I-restricted CD8 + CTL response in mice with a single subcutaneous immunization, whereas non-coated liposomes do not. Since no damage to the skin at the injection site was caused by the liposomes, and since the oligomannose-coated liposomes consist of innocuous materials ubiquitously distributed throughout the human body, they may be highly suitable for use as a safe adjuvant in vaccines inducing a CTL response against HIV.