Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals. Vaccination against FMD is a routine practice in many countries where the disease is endemic. This study was designed first to investigate the extract of the seeds of Momordica cochinchinensis (Lour.) Spreng. (ECMS) for its adjuvant effect on vaccination of inactivated FMDV antigens in a guinea pig model and then to evaluate the supplement of ECMS in oil-emulsified FMD vaccines for its immunopotentiation in pigs. The results indicated that ECMS and oil emulsion act synergistically as adjuvants to promote the production of FMDV-and VP1-specific immunoglobulin G (IgG) and subclasses in guinea pigs. A supplement of ECMS in a commercial FMD vaccine significantly enhanced FMDV-specific indirect hemagglutination assay titers as well as VP1-specific IgG and subclasses in pigs. Therefore, ECMS could be an alternative approach to improving swine FMD vaccination when the vaccine is poor to induce an effective immune response.Foot-and-mouth disease (FMD) is a highly contagious disease affecting cloven-hoofed animals, particularly domestic species, such as cattle, swine, and sheep. Financial losses due to FMD are huge, and it is believed to be the most economically important animal disease in the world (26). Vaccination against FMD is a routine practice in many countries where the disease is endemic. Most commercially available FMD vaccines are inactivated whole-virus preparations containing oil emulsions as an adjuvant to improve their efficacy. However, some FMD vaccines have been reported to induce poor immune responses. For example, Xie et al. (33) observed that only 20.9% of piglets produced immune responses with antibody titers high enough for protection following vaccination against FMD (type O) in the Ningxia province of China. Hao et al. (12) analyzed 91 serum samples of pigs having received vaccination against FMD (type O) and found that only 31.9% of the samples had antibody titers required for immune protection immunity. Therefore, there is a need to improve currently available FMD vaccines in order to effectively protect animals from FMD infection.Our previous research has demonstrated that a supplement of saponin extracted from the bark of Quillaja saponaria Molina (Quil A) in vaccines significantly enhances immune responses to FMD vaccination (32). However, Quil A may be limited in veterinary use because of its hemolytic activity (23). Another study has shown that an extract from a traditional Chinese medicine, the seeds of Momordica cochinchinensis (Lour.) Spreng. (ECMS), has an adjuvant effect on the immune responses elicited by ovalbumin (OVA), with a much lower hemolytic activity (30). ECMS has also been proven effective in enhancing immune responses to vaccination against avian influenza (H5N1) in chickens (24). The medical use of the seeds has been described in ancient Chinese medical literature, Kai Bao Materia Medica, from the Song Dynasty (AD 793) (10) and is currently included in both Chinese pharmacopoei...