Technical Abstract: Larkspur (Delphinium spp.) causes significant livestock losses in the western United States. The purpose of this study was to determine if larkspur toxins conjugated to protein carriers would promote an immunogenic response in animals to protect against the toxic effects of larkspur. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine if the resulting immunologic response altered animal susceptibility to methyllycaconitine, the major toxic larkspur alkaloid. Although vaccinations appeared to provide a mild protective effect against intravenous methyllycaconitine toxicity, the protective effect was not statistically significant when compared to the control group because of overlapping 95% confidence limits between the lethal dose of the vaccinated and control groups. There was a strong relationship, however, between antibody titer and mortality of mice vaccinated with the lycoctonine conjugate (LYC). In the LYC vaccinated group, mouse mortality was related (P = 0.001) to serum titers for methyllycaconitine challenge doses up to 4.5 mg/kg b.w. When mice with low antibody titers were removed from the vaccinated groups in which titer was related to mortality, the recalculated LD50s were 20% higher than the LD50s of the control group. This suggests that vaccination altered methyllycaconitine toxicity in mice and that vaccination may be useful in decreasing the effects of larkspur toxins in animals. Additional studies are warranted to continue development of potential larkspur vaccines for livestock.