QS-21 is a purified immunological adjuvant derived from a natural source, the bark of the tree Quillaja saponaria. It is a water soluble triterpene glycoside with amphiphilic character that can be mixed with a soluble antigen in a fully soluble vaccine formulation or combined with emulsion or mineral salt adjuvants. QS-21 has been shown to enhance antibody and cell-mediated immune responses to subunit antigens, as well as DNA vaccines in animal models. It acts as an immunostimulatory adjuvant, eliciting production of immunomodulatory cytokines, and not as an antigen depot. QS-21 is currently under clinical evaluation with various vaccines. This includes a Phase II evaluation of a QS-21 adjuvanted pneumococcal polysaccharide vaccine and a Phase III evaluation of a QS-21 adjuvanted GM2-KLH (ganglioside GM2 vaccine) immunotherapeutic product for melanoma. At present, more than 1600 individuals have received vaccines containing QS-21 adjuvant. In most studies, QS-21-containing vaccines have been well-tolerated. No serious adverse events have occurred.