Technical Abstract: Pyrrolizidine alkaloids (PAs) are plant toxins that poison livestock, wildlife and occasionally humans. We have developed several riddelliine (an unsaturated macrocyclic PA) conjugates for ELISA development. The purpose of this research is to test was to test if animals immunized with riddelliine-protein conjugates develop tolerance or resistance to riddelliine poisoning. Three groups of 30 weanling male rats were injected with two riddelliine conjugates or a sham ovalbumin conjugate. After a primary injection with complete Freund’s adjuvant, 2 boosters using incomplete Freund’s adjuvant were used. The immunized rats were divided into groups of 10 rats that were dosed via oral gavage with riddelline at doses of 5 mg/kg (25% LD50), 15 mg/kg (75% LD50) and 30 mg/kg (150% LD50) for 10 days. After dosing, the rats were euthanized; serum was collected; and tissues were collected, fixed and processed for histologic studies. Post mortem titers showed great variation in animal response to vaccination. Though there was little biochemical or histologic difference between the vaccination groups, the hepatic lesions appeared to be less severe in animals that had high titers. This suggests the immunization may alter riddelliine toxicity but additional studies are needed to verify this change.