Quillaja saponins (Q. saponins) are readily hydrolyzed at neutral pH to yield degraded deacylated saponins (DS-saponins). Degradation of Q. saponins resulted in some reduction of their capacity to elicit IgG1, IgG2a and IgG2b isotypes against the highly immunogenic envelope glycoprotein D (gD) from herpes simplex virus, type 1 (HSV-1). Addition to gD of a dose of DS-saponins tenfold higher than the original Q. saponins dose stimulated lower IgG2a and IgG2b titers than those obtained with gD alone or combined with native saponins. However, the IgG1 response was somewhat similar in all the groups. In contrast, Q. saponins' deacylation resulted in a significant reduction in both the production of HSV-1 neutralizing antibodies and survival rates after viral challenge. Vaccination with gD alone did not protect mice against a lethal challenge with HSV-1, while the addition of Q. saponins to gD resulted in protection against HSV-1. Vaccines containing partially deacylated saponins yielded lower survival rates, while vaccines containing DS-saponins did not protect mice against HSV-1. Increasing the dose of DS-saponins tenfold resulted in a marginal increase in protection. These results show that degradation of Q. saponins during storage can have a deleterious effect on vaccines' efficacies. © 2002 Published by Elsevier Science B.V.