Erysipelothrix rhusiopathiae, a gram-positive bacterium, is the causative agent of erysipelas in various animals, including cetaceans. The disease is of concern in marine mammal facilities because peracute septicemic infections can occur. Therefore, prevention of the disease, in particular by the use of vaccination, is important. Since a vaccine has not been developed for specific use in dolphins, a commercially available vaccine for use in swine is being utilized by oceanaria. Further, an appropriate scientifically based vaccination schedule has not been determined for dolphins. The objective of this study was therefore to characterize the humoral immune response of bottlenose dolphins to a commercially available E. rhusiopathiae vaccine for swine. An indirect ELISA for the measurement of antibody titers of bottlenose dolphins (Tursiops truncatus) was developed using newly generated dolphin Ig-specific monoclonal (MAb) and polyclonal (PAb) antibodies. For validation of the assay, serial blood samples (N = 26) from 3 dolphins were collected prior to first immunization and prior to each subsequent immunization. Each dolphin received an initial IM immunization, a first booster immunization 4 wks later and six-monthly booster immunizations (N = 3, 4 or 5 respectively), following the manufacturer's instructions. Although the intensity of the immune response varied between the individual dolphins, seroconversion was observed in all 3 animals using both the MAb and the PAb. No antibodies were detected 6 days after the first immunization, but were measurable by day 14, at which time the humoral immune response peaked. Circulating antibodies were short-lived, as antibody titers waned as early as 114 ( x = 157 ± 31) days after immunization. However, an anamnestic immune response was observed in 2 out of 3 dolphins. The humoral immune response of dolphins to the vaccine antigen is very similar to the response reported in swine. While antibody titers of swine declined by 10 wks after immunization, 75% of the pigs were protected from a challenge infection 20 weeks after immunization. Until more information is available, we recommend an immunization schedule consisting of an initial immunization, a second immunization at 4 wks, followed by six-monthly booster immunizations. Further work is ongoing to evaluate cross-reactivity of the vaccine antigen with the dolphin E. rhusiopathiae strains.