The gram-negative, anaerobic bacterium Porphyromonas gingivalis, has been implicated in the etiology of adult periodontal disease. Among the potential virulence factors of this bacterium, the non-fimbrial adhesin hemagglutinin B (HagB) appears to be involved in the initial adherence of the bacteria to host tissue and the induction of anti-HagB antibody responses affords some protection from experimental alveolar bone loss. In the present study, we have investigated the ability of the quillaja saponin derivative GPI-0100 to act as an immunostimulant of responses to HagB following subcutaneous (s.c.) or intranasal (i.n.) immunization of mice. We have also compared the immunopotentiating ability of GPI-0100 with that of five other adjuvants. Evidence is provided that GPI-0100 was more effective than monophosphoryl lipid A and alum in inducing serum anti-HagB responses following s.c. immunization. A comparison of the responses induced following i.n. immunization with HagB and adjuvant revealed that the heat-labile toxin of Escherichia coli (LT) and the non-enzymatic mutant LT (E112K), followed by GPI-0100 potentiated higher serum and mucosal anti-HagB antibody responses, which in most cases were higher than those seen with the other adjuvants tested (i.e. monophosphoryl lipid A, alum and the B subunit of cholera toxin). Furthermore, a difference was seen in the nature of the serum IgG anti-HagB response based on the adjuvant used and route of immunization. These results demonstrate the effectiveness of GPI-0100 as both a systemic and mucosal adjuvant and support its potential use in the development of vaccines against periodontal, as well as other pathogens. © 2003 Elsevier Ltd. All rights reserved.